Autonomic Nervous System - Apex Flashcards

1
Q

Examples of positive feedback control in the human body include: (Select 3).:
a. generation of an AP
b. PaCO2 regulation
c. coagulation cascade
d. core temperature
e. serum glucose concentration
f. childbirth

A

A, F, and C

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2
Q

Homeostasis is a steady-state condition that comes with a price - it requires ____ to maintain the system.

A

energy

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3
Q

What does a negative feedback system dO?

A

Reverse a disturbance in some factors and leads to stability

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4
Q

What does a positive feedback system do?

A

Enhances or accelerates a disturbance in some factors and usually leads to instability

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5
Q

Any physiologic system that needs to be maintained in a normal range (set point) requires a ____.

A

control system

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6
Q

What four things must a control system be able to do:

A
  1. sense the regulated variable
  2. compare the input signal with an internal reference/set point
  3. Multiply the error signal by a proportionality coefficient (the gain) to produce an output signal
  4. adjust the important factor by activating an effector system
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7
Q

What is the most common control system for maintaining homeostasis?

A

A closed negative feedback loop

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8
Q

What are the sensors for the regulated variable - PaCO2?

A

central chemoreceptors

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9
Q

CO2 is hydrated in the ____, forming ____ which spontaneously dissociates into ___ and ___.

A

CSF; H2CO3; H+ and HCO3-

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10
Q

The PaCO2 is directly reflected by the ____, which is detected by central chemoreceptors in the _____ of the _____.

A

H+; retrotrapezoid nucleus of the medulla

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11
Q

What is the feedback controller for PaCO2?

A

Dorsal respiratory group (DRG)/central pattern generator (CPG)

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12
Q

What are the effectors for the regulated variable - PaCO2?

A

muscles of inspiration

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13
Q

An increased PaCO2 (the disturbance) results in a decreased PaCO2. What type of system is this?

A

A negative feedback control system

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14
Q

What is the sensor for the regulated variable - cervical opening?

A

Stretch receptors in the cervix

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15
Q

During L&D, sensory impulses from the stretch receptors in the cervix are sent to the _____.

A

hypothalamus

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16
Q

What is the feedback controller for the regulated variable - cervical opening?

A

The periventricular and supraoptic nuclei of the hypothalamus

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17
Q

Increased stretch impulses from the cervix received at the hypothalamus stimulate the _______ to release more _____.

A

posterior pituitary (neurohypophysis); oxytocin

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18
Q

What are the effectors for the regulated variable - cervical opening?

A

Oxytocin and the myometrium

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19
Q

Oxytocin binds to G protein-coupled receptors (Gq) on the _____, producing more ______.

A

myometrium; powerful uterine contractions

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20
Q

The fetus pushing more forcefully against the cervix and stimulating more oxytocin release is an example of which type of system?

A

Positive feedback cycle system

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21
Q

Oxytocin also stimulates _____ production by the uterine lining.

A

prostaglandin

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22
Q

Negative feedback or positive feedback??

Control of serum sodium concentration

A

Negative feedback

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23
Q

Negative feedback or positive feedback??

Enhances or accelerates a disturbance in a vital parameter

A

Positive feedback

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24
Q

Negative feedback or positive feedback??

Propagation of an AP

A

Positive feedback

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25
Q

Negative feedback or positive feedback??

Leads to stability in a vital parameter

A

Negative feedback

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26
Q

Negative feedback or positive feedback??

Leads to instability in a vital parameter

A

Positive feedback

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27
Q

Negative feedback or positive feedback??

Opposes or reverses a disturbance in a vital parameter

A

Negative feedback

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28
Q

Which method of cell signaling occurs when a cell responds to a chemical signaling molecule that the cell itself produced and secreted?
a. endocrine signaling
b. paracrine signaling
c. neurotransmitter signaling
d. autocrine signaling

A

D - autocrine signaling

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29
Q

What is the intracellular response to extracellular signals called?

A

Cell signaling/signal transduction

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30
Q

The conversion of info into a chemical change is called _____, a universal property of living cells.

A

signal transduction

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31
Q

Info arrives at cells in what 4 forms:

A
  1. Purely physical (energy)
  2. Chemical
  3. Cellular
  4. Extracellular matrix molecules
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32
Q

What are examples of purely physical/energy forms?

A

light, sound, heat, pressure, electricity

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33
Q

What are examples of chemicals?

A

NT, hormones, eicosanoids, drugs, toxins

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34
Q

What are examples of a cellular form of information arriving at cells?

A

Gap junctions

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35
Q

What are extracellular matrix molecule examples?

A

Collagen (think of PLT adhesion), integrins, laminin

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36
Q

What are the 3 main methods of intracellular communication?

A
  1. endocrine
  2. paracrine
  3. autocrine
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37
Q

Endocrine cell signaling = _________

A

a signaling molecule (i.e., a hormone) is secreted by an endocrine cell and transported through the circulation where it acts on a distant target cell

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38
Q

What is neuroendocrine signaling?

A

A specific type of endocrine signaling, where a neuron is the source of the hormone secreted into the blood

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39
Q

What is an example of neuroendocrine signaling?

A

The adrenal medulla releases epinephrine that binds to B1 receptors on the heart

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40
Q

What is paracrine signaling?

A

A chemical signaling molecule is released by one cell and acts locally to regulate the behavior of a neighboring cell

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41
Q

_____ cell signaling is a specific form of paracrine signaling.

A

Neurotransmitter

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42
Q

What is autocrine signaling?

A

A cell responds to a signaling molecule that it also produced.

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43
Q

NE binding to a presynaptic A2 receptor on the same nerve terminal that released NE is an example of what type of signaling?

A

Autocrine

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44
Q

What does autocoids mean?

A

Local hormone

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45
Q

Where are autocoids and paracrine hormones produced?

A

Locally

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46
Q

Autocoids and paracrine hormones are released in smaller or larger quantities than endocrine hormones?

A

Smaller

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47
Q

T/F: Autocoids and paracrine hormones are intended to act locally and are metabolized locally.

A

True

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48
Q

A chemical molecule that binds to a receptor and initiates a cellular response is called a:
a. second messenger
b. transducer
c. ligand
d. kinase

A

C - ligand

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49
Q

What does signal transduction exhibit?

A

specificity and sensitivity
amplification
integration
feedback
compartmentalization
desensitization

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50
Q

The flow of info in a signal transduction sequence follows _____ pathways.

A

Orderly

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51
Q

What are the 6 processes in signal transduction sequences?

A
  1. recognition
  2. transduction
  3. transmission
  4. modulation
  5. response
  6. termination
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52
Q

What are the 4 types of receptor-based signal transducers?

A
  1. transmembrane G protein-coupled receptors (GPCR)
  2. Transmembrane gated ion channels
  3. transmembrane enzyme-linked receptors
  4. Soluble nuclear (intracellular) receptors
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53
Q

______ is imparted by the cell-specific receptor and is mediated by the same kinds of weak, non-covalent forces the mediate enzyme-substrate interactions.

A

Specificity (selectivity)

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54
Q

Bonds ordered from weakest to strongest: ____ < _____ < ____ < ____ < _____

A

Van der Waals < hydrophobic < Hydrogen < ionic < covalent

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55
Q

When does amplification by enzyme cascade result?

A

When an enzyme associated with a signal receptor is activated, and in turn catalyzes the activation of many molecules of a second enzyme, which activates a third enzyme, and so on

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56
Q

What is integration?

A

The ability of a signal-transducing system to receive multiple signals and produce a unified response appropriate to the cell’s needs

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57
Q

Multiple components of signaling pathways are often brought together on _____ to increase their local concentration and effects.

A

Scaffold proteins

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58
Q

_____ are scaffolding proteins in addition to calcium channels.

A

Ryanodine receptors

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59
Q

When does desensitization occur?

A

When a signal is present continuously, desensitization of the receptor system results. (when the stimulus falls below a certain threshold, the system again becomes sensitive)

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60
Q

What is the general flow of info through G protein-coupled receptor signal transduction pathways?

A

1st messenger –> receptor –> effector –> 2nd messenger –> cellular response

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61
Q

The 1st step of signaling sequences is ____.

A

recognition of the signal by its receptor

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62
Q

All receptors are _____

A

proteins

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63
Q

A general term for any chemical that binds to a receptor is what?

A

Ligand (note - ligand immediately implies that there’s a receptor involved)

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64
Q

A ligand is also called what?

A

the first messenger

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65
Q

What initiates the signaling sequence?

A

Energy from the stimulus-receptor interaction causes a conformational change in the receptor and then initiates the signaling sequence

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66
Q

What is the second stage of the signaling sequence?

A

TRANSDUCTION of the extracellular message into an intracellular signal or 2nd messenger

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67
Q

The conformational change of a receptor triggers either _____ or causes the receptor to _____.

A

catalytic activity intrinsic to the receptor; interact with membrane or cytoplasmic enzymes

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68
Q

The final consequence of RECOGNITION + TRANSDUCTION is the generation of a _____ or the activation of a _____.

A

second messenger; catalytic cascade

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69
Q

What messengers are extracellular signals?

A

1st

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70
Q

What messengers are intracellular signals?

A

2nd

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71
Q

_____ are extracellular signals, ____ are intracellular signals.

A

1st messengers; 2nd messengers

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72
Q

What occurs are tranduction?

A

TRANSMISSION

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73
Q

What is transmission during the signal sequence?

A

The second messenger’s signal to the appropriate effector(s)

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74
Q

T/F: There are multiple pathways for signal transmission.

A

True

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75
Q

What are some key activities in signal transmission pathways?

A
  1. activation of kinases that add phosphates to proteins
  2. release or sequestration of intracellular ions
  3. regulation of metabolic processes
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76
Q

____ and _____ typically occur during transmission

A

Amplification and integration

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77
Q

What stage of the signaling sequence does amplification typically occur?

A

Transmission

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78
Q

What stage of the signaling sequence does integration typically occur?

A

Transmission

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79
Q

What occurs after transmission?

A

MODULATION of downstream chemicals

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80
Q

What are two common modulation/”on/off” events?

A

enzymatic phosphorylation or dephosphorylation

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81
Q

What occurs after modulation?

A

RESPONSE of the cell to the initial stimulus

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82
Q

What are the different types of responses?

A

proliferation, differentiation, cell movement, metabolism, cell behavior

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83
Q

What occurs after the response stage of the signal sequence?

A

TERMINATION of the response

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84
Q

How is termination often accomplished?

A

feedback control

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85
Q

What is ATP?

A

adenosine triphosphate

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86
Q

What is IP3

A

Inositol triphosphate

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87
Q

Phenylephrine is a ____ for the ____ receptor.

A

ligand/agonist/first messenger; alpha-1

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88
Q

____ is a ligand for purinergic receptors.

A

ATP / adenosine

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89
Q

What is an example of a drug that has an extracellular target?

A

Dabigatran

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90
Q

What is an example of a drug that has an adhesion molecules?

A

Eptifibatide

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91
Q

ID the 4 categories of receptor-based signal transducers.

A
  1. G protein coupled receptors
  2. Gated ion channels
  3. Enzyme-linked receptors
  4. Soluble nuclear receptors
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92
Q

What is another name for a chemical that binds to a receptor?

A

ligand

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93
Q

What family of enzymes catalyzes the addition of a phosphate group to a molecule?

A

Kinases

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94
Q

What chemical messengers are derived from arachidonic acid? (select 3)
a. prostaglandins
b. thyroxine
c. aldosterone
d. leukotrienes
e. dopamine
f. anadamide

A

A - prostaglandins
D - leukotrienes
F - anandamide

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95
Q

Most chemical signals fall into 4 categories of molecules:
1. ______
2. ______
3. ______
4. ______

A
  1. small hydrophilic molecules
  2. lipophilic molecules
  3. peptides and proteins
  4. others
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96
Q

Where are small hydrophilic molecules, peptides, and protein messengers stored?

A

In vesicles inside the cells that synthesize these molecules

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97
Q

______, _____, ____, and _____ are molecules that are not stored in vesicles.

A

Lipophilic molecules, purine, gas, and endocannabinoid messengers

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98
Q

Chemical messenger molecules bind to either _____ receptors or ____ receptors.

A

cell-surface or intracellular (cytoplasmic or nuclear)

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99
Q

What are the small hydrophilic chemical messenger classes?

A

Amino acids
BIogenic amines
choline esters
iodothyronines

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100
Q

What are 4 examples of amino acids?

A
  1. glycine
  2. glutamate
  3. GABA (y-aminobutyric acid)
  4. aspartate
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101
Q

What are 5 examples of biogenic amines?

A
  1. dopamine
  2. norepineprhine
  3. epinephrine
  4. serotonin (5-HT)
  5. histamine
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102
Q

What is an example of choline esters?

A

acetylcholine

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103
Q

What are 2 examples of idothyronines?

A
  1. thyroxine (T4)
  2. triiodothyronine (T3)
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104
Q

Small hydrophilic molecules are polar molecules are are ____ at physiologic pH.

A

ionized.

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105
Q

Do small hydrophilic chemical messengers readily cross plasma membranes?

A

No - therefore needs cell-surface receptors

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106
Q

____ of an amino acid precursor is a theme.

A

Decarboxylation

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107
Q

What 4 things are derived from tyrosine?

A
  1. dopamine
  2. NE
  3. Epi
  4. iodothyronines
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108
Q

T/F: GABA and glutamate can be intercoverted.

A

True

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109
Q

How are small hydrophilic chemical messengers typically released?

A

exocytosis (exception is T3&T4)

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110
Q

T3 and T4 are released through a ____

A

transporter

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111
Q

What are the 3 types of lipophilic chemical messengers?

A
  1. steroids
  2. eicosanoids
  3. miscellaneous
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112
Q

Vitamin D3 and retinoids are _____ messengers.

A

Lipophilic (nonpolar)

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113
Q

Prostaglandins are _____

A

eicosanoids

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114
Q

Leukotrienes are _____

A

eicosanoids

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115
Q

Thromboxanes are _____

A

Eicosanoids

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116
Q

Steroids are derived from what?

A

cholesterol

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117
Q

How do steroids circulate in the blood?

A

bound to a protein

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118
Q

T/F: Steroids can diffuse through the lipid bilayer of plasma membranes.

A

True

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119
Q

Where do steroids to receptors of target cells?

A

in the cytoplasm or nucleus of target cells

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120
Q

What are eicosanoids derived from?

A

polyunsaturated fatty acids w/ 18, 20, and 22 carbons

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121
Q

_______ is the main precursor of eicosanoids.

A

Arachidonic acid (20 carbons)

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122
Q

Eicosanoids primarily have endocrine, autocrine, or paracrine actions?

A

autocrine and paracrine

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123
Q

T/F: Unlike steroids, eicosanoids usually bind to cell surface receptors.

A

True

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124
Q

What is calcitriol, 1,25-dihydroxycholecalciferol?

A

Vitamin D3

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125
Q

What is 1,25(OH)2D3?

A

Vitamin D3

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126
Q

______ is a cholesterol derivative but it does not retain the cholesterol ring structure.

A

Vitamin D3

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127
Q

Do steroids retain the cholesterol ring strucutre?

A

Yes

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128
Q

Retinoids are derived from what?

A

Vitamin A

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129
Q

Retinoids play a role in ______.

A

growth and development

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130
Q

Peptides and protein chemical messengers are generally ____ molecules.

A

hydrophilic (polar)

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131
Q

Peptides and protein chemical messengers do or do not readily cross plasma membranes?

A

Do not

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132
Q

How do peptides and protein chemical messengers circulate in the bloodstream?

A

As unbound molecules

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133
Q

____ and _____ are nucleotides and nucleosides.

A

ATP and Adenosine

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134
Q

Adeonsine and ATP are _____.

A

purines

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135
Q

T/F: Adenosine and ATP are stored in vesicles.

A

False

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136
Q

CO and NO are or are not lipid soluble?

A

Are

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137
Q

What kind of action do CO and NO have?

A

paracrine

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138
Q

What is NO synthesized from?

A

amino acid L-arginine

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139
Q

NO and CO serve as ____ neurotransmitters.

A

Retrograde

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140
Q

Anandamide (AEA) and 2-arachidonylgycerol (2-AG) are what type of chemical messengers?

A

Endocannabinoids

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141
Q

What are endocannabinoids derived from?

A

arachidonic acid

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142
Q

What receptors do endocannabinoids bind to?

A

CB-1 (CNS) and CB-2 (peripheral)

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143
Q

Endocannabinoids are lipophilic or hydrophilic?

A

Lipophilic

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144
Q

CB-1 and CB-2 are _____ receptors.

A

G protein-coupled

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145
Q

The brain has more _____ receptors than any other type of G protein-coupled recetpor!

A

cannabinoid

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146
Q

Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???

Insulin - ___________

A

Peptide and protein molecules

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147
Q

Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???

NO - ___________

A

Lipophilic

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148
Q

Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???

Angiotensin II - ___________

A

Peptide and protein

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149
Q

Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???

Thyroxine - ___________

A

Hydrophilic

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150
Q

Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???

Calcitriol - ___________

A

Lipophilic

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151
Q

Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???

Substance P - ___________

A

Peptide and protein

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152
Q

Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???

GABA - ___________

A

Hydrophilic

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153
Q

Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???

Aldosterone - ___________

A

Lipophilic

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154
Q

Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???

Acetylcholine - ___________

A

Hydrophilic

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155
Q

Which categories of signaling molecules are stored in vesicles in the cell that synthesized the molecules?

A
  1. small hydrophilic chemical messengers
  2. peptide and protein chemical messengeres
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156
Q

Which lipophilic chemical messengers are not derived from cholesterol?

A

eicosanoids, retinoids, endocannabinoids

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157
Q

Dopamine, Epi, NE, and the idothyroinines are derived from which amino acid?

A

Tyrosine

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158
Q

How many times does a G protein-coupled receptor span the plasma membrane?

A

7

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159
Q

What is the largest and most diverse family of receptors on the cell surface?

A

G protein coupled receptors (GPCR)

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160
Q

What ligands bind to GPCRs?

A

NT, hormones, vasoactive peptides, odorants, tastants, and local chemical factors

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161
Q

About ___ to ___ of all drugs target GPCR.

A

1/2 to 2/3

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162
Q

G proteins are molecular switches and can _____ themselves through inherent GTPase activity in the ____ subunit.

A

inactivate; alpha

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163
Q

In the GPT-loaded state, the ____ interacts with downstream effects. What may also interact with downstream effectors?

A

alpha subunit; beta-gamma complex

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164
Q

What are the 4 G protein families?

A
  1. Gs (stimulatory)
  2. Gi (inhibitory)
  3. Gq
  4. G12,13
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165
Q

What does the following represent?

Ligand –> GPCR –> Effector –> 2nd messenger –> Cell Resposne

A

The sequence of signal transduction through GPCR

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166
Q

What 3 essential components characterize signal transduction through GPCRs?

A
  1. plasma membrane receptor with 7 transmembrane helical segments
  2. A guanosine nucleotide-binding protein (g protein) activates the effector enzyme/path
  3. An effector (usually enzyme) generates 2nd messenger
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167
Q

GPCRs have a plasma membrane receptor with _______ transmembrane ___ segments.

A

7; helical
(7-TM seven-helix or serpentine receptor)

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168
Q

What do G proteins link?

A

receptor activation with a variety of downstream effects

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169
Q

The ___ class of G proteins are associated with 7-TM receptors.

A

Heterotrimeric (αβᵞ subunits)

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170
Q

When are G proteins turned ON?

A

when a ligand binds to the receptor binding site

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171
Q

When are G proteins turned OFF?

A

By the intrinsic GTPase activity in the alpha subunit

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172
Q

GDP is bound to the ____ subunit.

A

alpha

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173
Q

When activated, the 𝜶βᵞ complex of GPRC disassembles into a free GTP bound ___ subunit and a separate ___ complex.

A

𝜶; βᵞ

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174
Q

A _____ will stimulate (or inhibit) the production of a second messenger that will ultimately produce a change in cellular function.

A

G𝜶 subunit

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175
Q

Major effector targets of G𝜶 subunits include: (3)

A
  1. adenylate cyclases (AC)
  2. Phospholipase C (PLC)
  3. Phospholipase A2 (PLA2)
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176
Q

T/F: The βᵞ complex can interact with down stream effectors.

A

True

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177
Q

What are major effector targets for Gβᵞ subunits? (3)

A
  1. Gi, 0-regulated potassium channels (GIRK)
  2. voltage-gated calcium channels
  3. beta-adrenergic receptor kinase (BARK)
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178
Q

The alpha subunit has intrinsic GTPase activity, which catalyzes the hydrolysis of GTP to ___ and ___.

A

GDP and Pi

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179
Q

Gs stimulates _____

A

adenylyl cyclase

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180
Q

Gi inhibits ____

A

adenylyl cyclase

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181
Q

Cq11 stimulates _____

A

phospholipase C (PLC)

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182
Q

C12,13 activates ______

A

small G proteins

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183
Q

____ toxin chemically alters the Gs subunit to inhibit the intrinsic GTPase activity.

A

Cholera

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184
Q

Cholera inhibits the intrinsic GTPase activity. What occurs because of this?

A

continuous activation of the G protein and adenylate cylcase –> cell is swamped with cAMP –> stimulation of the export of fluid across the intestinal epithelium

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185
Q

____ toxin chemically alters the Gi,0 subunit

A

Pertussis

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186
Q

McCune-Albright syndrome is characterized by defects of ______.

A

hormonal regulation

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187
Q

What causes McCune-Albright syndrome?

A

A gain-of-function mutation of Gs that correlates w/ a massive disturbance of Gs controlled. hormone production

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188
Q

What causes pseudohypoparathyroidism?

A

A loss-of-function mutation of Gs (results in effects of PTH being suppressed –> premature puberty w/ obesity, growth retardation, and skeletal deformities)

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189
Q

G-alpha subunit target effector OR G-beta/gamma subunit target effector???

Adenylyl cyclase

A

alpha

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190
Q

G-alpha subunit target effector OR G-beta/gamma subunit target effector???

Phospholipase C

A

alpha

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191
Q

G-alpha subunit target effector OR G-beta/gamma subunit target effector???

Voltage-gated Ca channels

A

beta/gamma

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192
Q

G-alpha subunit target effector OR G-beta/gamma subunit target effector???

Gi,0-regulated potassium channels

A

beta/gamma

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193
Q

G-alpha subunit target effector OR G-beta/gamma subunit target effector???

Phospholipase A2

A

alpha

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194
Q

G-alpha subunit target effector OR G-beta/gamma subunit target effector???

Beta-adrenergic receptor kinase

A

beta/gamma

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195
Q

Which heterotrimeric G-protein subunit contains the intrinsic GTPase activity?

A

alpha

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196
Q

Match each enzyme with the substrate –> second messenger reaction the enzyme catalyzes.

Phospholipase A2, Adenylyl Cyclase, and Phospholipase C

ATP –> cAMP
PIP2 –> IP3 + DAG
Phospholipid –> arachidonic acid

A

Phospholipase A2 + Phospholipid –> arachidonic acid

Adenylyl Cyclase + ATP –> cAMP

Phospholiapse C + PIP2 –> IP3 + DAG

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197
Q

GPCRs target what # of downstream effectors that produce second messengers?

A

3

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198
Q

Adenylyl cyclase —> ___________

A

cyclic adenosine monophostate (cAMP)

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199
Q

PHospholipase C (PLC) —> _________

A

inositol triphosphate (IP3) & diacylglycerol (DAG)

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200
Q

Phospholipase A2 (PLA2) –> ________

A

Eicosanoids (20-carbon lipid mediators)

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201
Q

T/F: Second messenger effects are tissue specific.

A

True

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202
Q

Second messenger effects are ____ specific.

A

tissue

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203
Q

____ plays a key role int he regulation of intracellular signal transduction.

A

cAMP

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204
Q

The intracellular effects of cAMP are mediated by the enzyme _________, ____.

A

cAMP-dependent protein kinase, PKA

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205
Q

_____ is a second messenger that leads to Ca2+ release from intracellular storage sites.

A

IP3 (inositol-1,4,5,-triphosphate)

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206
Q

Many downstream signaling events mediated by Ca2+ are modulated by a Ca2+ sensing and binding protein, _____.

A

calmodulin (CaM)

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207
Q

What is the function of adenylyl cyclase?

A

To convert ATP to cyclic adenosine monophosphate (cAMP)

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208
Q

IP3 and DAG are ____ messengers

A

second

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209
Q

___ together with ___ activates PLC

A

Gq,11 & Ca2+

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210
Q

IP3 binds to what channels and where?

A

Ca2+ channels on the endoplasmic reticulum

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211
Q

What is released after IP3 binds to a channel?

A

Calcium

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212
Q

DAG in the membrane acts as a docking site for and activator of _____.

A

protein kinase C (PKC)

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213
Q

Phospholipase A2 is a ___ dependent enzyme.

A

Ca2+

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214
Q

Phospholipase A2 liberates what from the cell membrane?

A

Arachidonic acid

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215
Q

Arachidonic acid is the precursor to how many families of lipid signaling. molecules?

A

3

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216
Q

What 3 lipid signaling molecules is arachidonic acid the precursor to?

A
  1. Prostaglandins and thromboxanes (porstanoids)
  2. Leukotrienes
  3. CYP450 monooxygenases
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217
Q

CYP450 monoxygenases catalyze the formation of ____ and ____ from the ____ substrace.

A

HETEs (hydroxyeicosatetraenoic acid); EET (cis-epoxyeicosatrienoic acid); arachidonic acid

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218
Q

Leukotrienes are generated when ___ encounters lipoxygenase.

A

arachidonic acid

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219
Q

Prostaglandins and thromboxanes are produced by the initial action of ____ on the arachidonic acid substrate.

A

cyxlooxygenases

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220
Q

Prostanoids, leukotrienes, HETEs, and EETs are collectively called _____.

A

Eicosanoids

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221
Q

In cardiac myocytes, increased cAMP does what?

A

enhances contractiliy

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222
Q

In cardiac myocytes, increased cAMP enhances contractility (____ receptors effects).

A

Beta-1

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223
Q

_____ messenger effects are tissue-specific.

A

Second

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224
Q

In smooth muscle of airways and vessels, increased cAMP causes _______.

A

relaxation and dilation.

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225
Q

In smooth muscle of airways and vessels, increased cAMP causes relaxation and dilation (_____ receptor effects).

A

Beta-2

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226
Q

In PLTs, increased cAMP _____.

A

reduces PLT aggregation

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227
Q

In principal cells of the nephron, increased cAMP ___________________.

A

promotes insertion of aquaporin-2 water channels in the apical membrane

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228
Q

Think of ____ as the sensors of second messengers.

A

protein kinases

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229
Q

What are kinases?

A

Enzymes that catalyze the addition of phosphate groups (PO4 -2) to their substrate

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230
Q

What are common tragets for kinases?

A

downstream proteins

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231
Q

_____ catalyze the removal of phosphate groups from their substrate.

A

Phophatases

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232
Q

cAMp activates ____ to modify cellular function.

A

protein kinase A (PKA)

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233
Q

Protein Kinase A (PKA) contains 2 _____ and 2 _____.

A

regulatory subunits; catalytic subunits

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234
Q

What happens when cAMP binds to the regulatory subunits of PKA?

A

It causes dissociation of the catalytic subunits

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235
Q

What are the catalytic subunits of PKA?

A

Serine/threonin (Ser/Thr) kinases

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236
Q

What terminates the action of cAMP?

A

Phosphodiesterases

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237
Q

What terminates the action of protein kinases?

A

Protein phosphatases

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238
Q

DAG is lipophilic or hydrophilic?

A

Lipophilic

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239
Q

DAG and Ca2+ activate what?

A

Protein Kinase C (PKC)

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240
Q

What cellular functions is PKC involved in? (its a lot….)

A
  1. receptor desensitization
  2. modulating membrane structure events
  3. regulating transcription
  4. mediating immune responses
  5. regulating cell growth
  6. learning and memory
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241
Q

When is the action of DAG terminated?

A

When the molecule is recycled into new phospholipids

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242
Q

IP3 is the ___ messenger that liberates ___ from intracellular storage sites.

A

second; Ca2+

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243
Q

Ca2+ is released from ER into the ____, resulting in a dramatic increase in intracellular or extracellular Calcium?

A

cytoplasm; intracellular

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244
Q

A high _____ activates several Ca2+ dependent protein kinases and phosphatases.

A

cytosolic [Ca2+]

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245
Q

Ca2+ signals are terminated by ATP-dependent processes:
1. ______________________
2. _______________________

A

Ca2+ is returned into the ER
Ca2+ is pumped out of the cell

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246
Q

When is the action of IP3 terminated?

A

when the molecule is recycled into new phophoslipids

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247
Q

Freely available intracellular Ca2+ is a ____ messenger.

A

2nd

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248
Q

_____ is directly or indirectly involved in most cell processes, from fertilization of the ovum to cell death.

A

Intracellular Ca2+

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249
Q

Unlike other second messengers, ____ is NOT synthesized, liberated from a precursor molecule, or activated by enzymes.

A

Calcium (it is the increased intracellular Ca2+ that is the signal)

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250
Q

What are the sources of Cytoplasmic Ca2+? (6)

A
  1. voltage-gated Ca channels
  2. storage- operated Ca channels
  3. nonselective TRP ion channels
  4. ionotropic NT receptors (NMDA)
  5. IP3-controlled Ca channels (ER)
  6. RyR Ca selective channels
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251
Q

Downstream Target of Ca2+:

Voltage-gated calcium channels - _____

A

proteins that buffer calcium - calmodulin and calsequestrin

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252
Q

Downstream Target of Ca2+:

storage-operated calcium channels - _____

A

Calcium sensor proteins (camodulin, troponin C, synaptotagmin [presynaptic vesicle exocytosis])

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253
Q

Downstream Target of Ca2+:

Nonselective TRP ion channels - _____

A

enzymes (PLA2, PKC, NO synthases)

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254
Q

Downstream Target of Ca2+:

Ionotropic NT receptors (NMDA) - _____

A

Receptors and ion channels: IP3 receptors, RyRs, Ca-activated K and Cl channels

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255
Q

Removal of cytoplasmic reticulum….
voltage-gated calcium channels = _________

A

Na+-Ca2+ Exchanger (NCX) at the plasma membrane

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256
Q

Removal of cytoplasmic reticulum….
storage-operated calcium channels = _________

A

Ca2+-ATPase (“pump”) at the plasma membrane (PMCA)

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257
Q

Removal of cytoplasmic reticulum….
Nonselective TRP ion channels = _________

A

Ca2+-ATPase at the sarcoplasmic (muscle) or endoplasmic reticulum (SERCAs)

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258
Q

What Ca2+ sending and binding protein modulates may downstream events mediated by Ca2+?

A

Calmodulin (CaM)

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259
Q

When intracellular Ca2+ concentration increases, _____ Ca2+ binds to CaM inducing a major conformation change to the protein.

A

3-4

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260
Q

The active Ca2+/CaM complex has a wide range of downstream targets including:
1.
2.
3.
4.

A
  1. NO synthase
  2. Ca2+/CaM dependent protein kinases (ex: myosin light-chain kinase)
  3. adenylyl cyclase
  4. cAMP-specific PDE
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261
Q

caMP, DAG, IP3, or iCa???

Lipid second messenger

A

DAG

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262
Q

caMP, DAG, IP3, or iCa???

Generated from PIP2 and stays in the plasma membrane

A

DAG

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263
Q

caMP, DAG, IP3, or iCa???

Targets ligand activated Ca channels on the ER

A

IP3

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264
Q

caMP, DAG, IP3, or iCa???

IP3 releases it from the ER

A

iCa

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265
Q

caMP, DAG, IP3, or iCa???

Removed from the cytoplasm by pumps and transporters

A

iCa

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266
Q

caMP, DAG, IP3, or iCa???

Generated from PIP2 and diffuses in the cytoplasm

A

IP3

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267
Q

caMP, DAG, IP3, or iCa???

Activates PKA

A

cAMP

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268
Q

caMP, DAG, IP3, or iCa???

Adenylyl cyclase catalyzes production

A

cAMP

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269
Q

caMP, DAG, IP3, or iCa???

ATP is the precursor

A

cAMP

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270
Q

Which G protein alpha subunit activates adenylyl cyclase?

A

G-alpha S activates adenylyl cyclase

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271
Q

Which 2 Ca transporters are found in the plasma membrane

A
  1. sodium-calcium exchanger (NCX)
  2. Ca2+ ATPase (pump, PMCA)
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272
Q

What enzyme family catalyzes the addition of a phosphate group to a substrate?

A

Kinases catalyze the addition of a phosphate group to their substrates

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273
Q

What enzyme produces IP3 and DAG from PIP2?

A

PLC (phopholipase C)

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274
Q

The 2 types of synpases in the human body are (select 2):
a. chemical
b. thermal
c. mechanical
d. electrical

A

A and D

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275
Q

_____ play a crucial role in AP and other electrical behavior of membranes.

A

Ion channels

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276
Q

Ion channels usually have what type of pores?

A

gated

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277
Q

What helps the nervous system get the right signal to the right place in the body at the right time?

A

An intercellular junction called the synpase

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278
Q

What are the two types of synapses?

A

electrical and chemical

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279
Q

____ synapses are far more prevalent and diverse.

A

Chemical

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280
Q

____ receptors are the key proteins of signal transduction at chemical synapses.

A

NT

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281
Q

NT receptors are transmembrane proteins that are either:
1. _____
2. _____

A
  1. ion channels (ionotropic receptors)
  2. coupled to heterotrimeric G proteins (metabotropic receptors)
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282
Q

____ synapses are polarized. What does this mean?

A

Chemical; primarily one-way communication

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283
Q

What are chemical synapses comprised of?

A

A presynaptic terminal, synaptic cleft, and postsynaptic membrane

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284
Q

What is the presynaptic terminal also called?

A

axon terminal, synaptic bouton, or synaptic knobs

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285
Q

How wide is the synaptic cleft on chemical synapses?

A

20-40 nm wide

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286
Q

Ion channels are integral membrane proteins that form ________ pores through which selected ions can pass.

A

water-filled pores

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287
Q

T/F: Ion channels exhibit ion selectivity.

A

True

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288
Q

What type of channels usually have gated pores?

A

Ion channels

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289
Q

What are the 3 different types of gated ion channels?

A
  1. voltage-gated (membrane)
  2. ligand-gated (chemical)
  3. Mechanically-gated (pressure/sensory receptors)
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290
Q

T/F: ALL ion channels are gated.

A

False - not all ion channels are gated

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291
Q

What is an example of an ion channel that is not gated?

A

“leaky” potassium channels that establish resting membrane potential

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292
Q

Chemical synapses convert a ____ signal ➡ a ____ signal through the release of NT.

A

electrical; chemical

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293
Q

Chemical synapses communicate messages in what direction?

A

one direction from the presynaptic membrane to the postsynaptic membrane, across the synaptic cleft

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294
Q

NT act as endocrine, paracrine, or autocrine messengers?

A

paracrine and autocrine messengers

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295
Q

NT act as 1st or 2nd messenger?

A

1st - they bind to receptors and generate electrical or biochemical signals in postsynaptic cells

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296
Q

What type of synapses allow bi-directional flow?

A

Electrical

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297
Q

At electrical synapses, cells are connected by what?

A

gap junctions

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298
Q

Gap junctions consist of 2 hemichannels called _____.

A

connexions

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299
Q

What allows the myocardial cells to depolarize synchronously?

A

intercalated discs in the heart that contain electrical synapses

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300
Q

All ionotropic receptors have ____ subunits whose arrangement defines a central pore.

A

4-5

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301
Q

When does ionotropic receptor activation cease?

A

When the NT dissociates from the receptor or when the receptor is desensitized

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302
Q

Ionotropic receptors participate in fast or slow synaptic responses?

A

Fast

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303
Q

What are metabotropic receptors?

A

7 transmembrane-spanning receptors coupled to heterotrimeric G proteins (GPCR)

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304
Q

Metabotropic receptors participate in ____responses compared to inotropic receptors.

A

slower (seconds to minutes); compared to milliseconds or faster

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305
Q

AChr, adrenergic receptors, GABAbR, opioid receptors, and 5-HT1R are all _____ receptors.

A

metabotropic

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306
Q

What receptors trigger biochemical cascade?

A

Metabotropic - tip it sounds like metabolism or metabolite… it activates enzymes

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307
Q

The presynaptic terminal of chemical synapses contain what 2 important organells?

A

Mitochondria
Synaptic vesicles

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308
Q

What is mitochondria’s job in presynaptic terminals?

A

provides ATP, biochemical intermediates, and enzymes for the syntehsis and degradation of NT

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309
Q

What is synaptic vesicles job in presynaptic terminals?

A

concentrate, store, and deliver NT at the synapse

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310
Q

Membrane depolarization causes _____ channels (N-type) to open, permitting Ca2+ ions to flow into the terminal.

A

Ca2+

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311
Q

Increased intracellular Ca2+ is sensed by _____ in the docking proteins complex. This triggers the fusion of vesicles with the presynaptic membrane. This process is _____.

A

synaptotagmin; exocytosis

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312
Q

NT molecules bind to either ____ or _____ receptors on the post-synaptic membrane, leading to a post-synaptic event.

A

ionotropic or metabotropic

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313
Q

Volatile anesthetics inhibit excitatory neurotransmission (via ___ and ____ receptors).

A

NMDA and nicotinic ACh

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314
Q

Volatile anesthetics enhance inhibitor neurotransmission (via ___ and ____ receptors).

A

GABA and glycine

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315
Q

What causes hyperpolarization?

A

outward current of K+,
Cl= influx,
closure of Ca2+ channels

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316
Q

What causes depolarizatin?

A

net inward current of:
Na+ influx
Ca2+ influx
Reduced K+ efflux through leaky channels

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317
Q

Ionotropic receptor OR metabotropic receptor???

Conformational change sets in motion a biochemical cascade

A

Metabotropic

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318
Q

Ionotropic receptor OR metabotropic receptor???

Slower synaptic response

A

Metabotropic

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319
Q

Ionotropic receptor OR metabotropic receptor???

Muscarinic AChR

A

Metabotropic

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320
Q

Ionotropic receptor OR metabotropic receptor???

5-HT3R

A

Ionotropic

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321
Q

Ionotropic receptor OR metabotropic receptor???

Conformational change gates a pore

A

Ionotropic

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322
Q

Ionotropic receptor OR metabotropic receptor???

Nicotinic AChR

A

Ionotropic

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323
Q

Ionotropic receptor OR metabotropic receptor???

Opioid Receptor

A

Metabotropic

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324
Q

Ionotropic receptor OR metabotropic receptor???

Fast synaptic response

A

ionotropic

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325
Q

List 2 gases that are unconventional NT.

A

NO
CO

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326
Q

What structure connects cells at an electrical synapse?

A

Gap junctions (connexions form gap junctions)

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327
Q

Which protein in the docking complex is the calcium sensor?

A

Synaptotagmin

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328
Q

Name 3 signals that open pores in gated ion channels.

A

Membrane voltage (electrical), chemicals (ligands), and pressure (mechanical)

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329
Q

Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional

DOPAMINE

A

Biogenic Amine

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330
Q

Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional

VASOACTIVE INTESTINAL PEPTIDE (VIP)

A

Neuropeptide

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331
Q

Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional

OPIOIDS

A

Neuropeptide

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332
Q

Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional

NOREPINEPHRINE

A

Biogenic Amine

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333
Q

Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional

ANANDAMIDE

A

Nonconventional

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334
Q

Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional

GLUTAMATE

A

Amino Acid

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335
Q

Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional

NITRIC OXIDE

A

Nonconventional

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336
Q

Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional

GLYCINE

A

Amino Acid

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337
Q

Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional

SUBSTANCE P

A

Neuropeptide

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338
Q

Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional

GABA

A

Amino Acid

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339
Q

Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional

SEROTONIN

A

Biogenic Amine

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340
Q

Where are nicotinic acetylcholine receptors NOT located?
a. autonomic ganglia
b. neuromuscular junction
c. chromaffin cells in the adrenal medulla
d. sinoatrial node

A

D - sinoatrial node

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341
Q

What is the primary NT of peripheral EFFERENT (motor) neural pathways?

A

Acetylcholine (ACh)

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342
Q

What role does Acetylcholine play in the CNS?

A
  • the modulation of sleep
  • wakefulness (in the RAS)
  • learning
  • memory
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343
Q

Where does Acetylcholine synthesis occur?

A

In the presynaptic nerve terminal

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344
Q

T/F: Cholinergic receptors can be ionotropic or metabotropic.

A

True

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345
Q

Are nicotinic ACh receptors ionotropic or metabotropic?

A

ionotropic

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346
Q

Are muscarinic ACh receptors ionotropic or metabotropic?

A

metabotropic

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347
Q

Cholinergic describes neurons or synapses that use ____ as the neurotransmitter.

A

Acetylcholine

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348
Q

Acetylcholine is the primary NT of peripheral efferent or afferent neural pathways?

A

EFFERENT

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349
Q

List all the places ACh is a NT at:
1.
2.
3.
4.
5.

A
  1. NMJ
  2. Autonomic ganglia
  3. Terminal synapses of parasympathetic postganglionic fibers
  4. Few sympathetic postganglionic fibers (sweat glands)
  5. NOn-neuronal cholinergic system (NNCS)
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350
Q

T/F: Only nicotinic receptors are expressed in the central neurons, not muscarinic receptors.

A

False - both are

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351
Q

What are the substrates of acetylcholine?

A

choline and acetyl-CoA

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352
Q

What is the rate-limiting factor for the availability of Acetylcholine?

A

The availability of its substrates (choline and acetyl-CoA)

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353
Q

How does glucose enter nerve terminals?

A

by passive transport (facilitated diffusion)

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354
Q

Glycolysis converts glucose to ______.

A

pyruvate

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355
Q

Where does glycolysis occur?

A

in the cytoplasm

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356
Q

An acetyl group from pyruvate is added to coenzyme A to produce _____.

A

acetyl-CoA

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357
Q

Choline is ______ transported into the presynaptic terminal.

A

actively

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358
Q

________ is the rate-limiting step in ACh synthesis.

A

Choline transport

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359
Q

What catalyzes the formation of ACh from acetyl-CoA + choline?

A

Choline acetyltransferase (ChAT)

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360
Q

Where is ACh stored?

A

In synaptic vesicles until release

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361
Q

How is ACh transported into vesciles?

A

By an H+-antiporter (exchanger)

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362
Q

_____ triggers vesicle fusion at the active zone, and ____ is released into the synaptic cleft by exocytosis.

A

Increased intracellular Ca2+; ACh

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363
Q

What hydrolyzes ACh? What is it hydorlyzed to?

A

Acetylcholinesterase (AChE); acetate + choline

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364
Q

What happens to the choline that is produced durign ACh hydrolysis?

A

It re-enters the nerve terminal and is reused for ACh synthesis

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365
Q

What is an antagonist of Ca2+ at the presynaptic nerve terminal?

A

Mg2+

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366
Q

Why does Mg2+ cause muscle weakness or potentiate NM block?

A

It is an antagonist of Ca2+ at the presynaptic nerve terminal

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367
Q

Nicotinic ACh recetpors (nAChR) are inotropic or metabotropic receptors?

A

Inotropic

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368
Q

T/F: nAChRs are nonselective anion channels.

A

F - nAChRs are nonselective cation channels.

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369
Q

Describe the structure of nAChRs.

A

They are pentameric complexes with 2 agonist binding sites - one at the extracellular 𝜶/ε interface of one 𝜶 subunit and the 𝜶/𝛅 interface of the other 𝜶 subunit

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370
Q

What is required to initiate the conformational change that opens the nAChR channels?

A

simultaneous binding of 2 ACh molecules to the alpha subunits

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371
Q

Where are NmAChRs found?

A

in skeletal muscle at the NMJ

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372
Q

Where are NnAChRs found?

A

in the autonomic ganglia, on the chromaffin cells of the adrenal medulla, and in the CNS

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373
Q

As their name implies, nAChR can be opened by the ____plant, _____.

A

tobacco plant, alkaloid nicotine

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374
Q

Muscarinic ACh receptors (mAChR) are inotropic or metabotropic receptors?

A

Metabotropic

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375
Q

Where are muscarinic AChRs found?

A

CNS, heart, smooth muscle, and glands of GI tract

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376
Q

_____ mediate most action of ACh in the CNS.

A

mAChR

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377
Q

Muscarinic AChRs are so named b/c they are activated by ____, a _____ found in a poisonous mushroom.

A

muscarine, a toxic alkaloid

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378
Q

How many types of mAChR have been identified?

A

5

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379
Q

Where are NM (nicotinic ACh) receptors found?

A

Skeletal muscle at NMJ

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380
Q

What is the signal transduction of NM (nicotinic ACh) receptors?

A

Opening of nonselective cation channels –> influx of Na

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381
Q

What is the response of activated NM (nicotinic ACh) receptors?

A

end-plate depolarization and skeletal muscle contraction

382
Q

Where are NN (nicotinic ACh) receptors found?

A

Autonomic ganglia, adrenal medulla, CNS

383
Q

Where are M1 (muscarinic ACh) receptors found?

A

autonomic ganglia

CNA

384
Q

Where are M2 (muscarinic ACh) receptors found?

A

Heart: nodal tissue
Heart: cardiac muscle

385
Q

Where are M3 (muscarinic ACh) receptors found?

A

Smooth muslce; GI

386
Q

Where are M4 (muscarinic ACh) receptors found?

A

CNS

387
Q

Where are M5 (muscarinic ACh) receptors found?

A

CNS

388
Q

What muscarinic receptors are found in the heart?

A

M2

389
Q

What muscarinic receptors are found in the GI tract?

A

M3

390
Q

What is the signal transduction of NN (nicotinic ACh) receptors?

A

Opening of nonselective cation channels –> influx of sodium

391
Q

What is the signal transduction of M1, M3, and M5 (muscarinic ACh) receptors?

A

Gq,11 –> PLC –> increased IP3 + increased DAG –> increased Ca2+ –> increased PKC

ALL ODD MUSCARINIC ARE COUPLED TO GQ

392
Q

What is the signal transduction of M2 and M4 (muscarinic ACh) receptors?

A

βᵞ subunit of Gi –> increased K+ channel (GIRK) opening

Gi –> inhibition of AC –> decreased cAMP

ALL EVEN MUSCARINIC ARE COUPLED TO Gi

393
Q

What is the response of activated NN (nicotinic ACh) receptors?

A

Depolarization of post-synaptic post-ganglionic neuron

Secretion of catecholamines

Arousal, attention, analgesia

394
Q

What is the response of activated M1 (muscarinic ACh) receptors?

A

Excitatory response

Arousal, attention, analgesia

395
Q

What is the response of activated M2 (muscarinic ACh) receptors?

A

Slowed spontaneous depolarization

DECREASES chronotropy, contracitlity, and domotropy

396
Q

What is the response of activated M3 (muscarinic ACh) receptors?

A

Contraction

Increased salivary secretions

397
Q

What is the response of activated M4 (muscarinic ACh) receptors?

A

Presynaptic autoreceptors –> negative feedback to supress ACh release

398
Q

What is the response of activated M5 (muscarinic ACh) receptors?

A

Promotes dopamine release, dilation of cerebral arteries

399
Q

Muscarinic AChR or Nicotinic AChR????

Binding of 2 Ach molecules for full activation

A

Nicotinic

400
Q

Muscarinic AChR or Nicotinic AChR????

Ionotropic

A

Nicotinic

401
Q

Muscarinic AChR or Nicotinic AChR????

NMJ

A

Nicotnic

402
Q

Muscarinic AChR or Nicotinic AChR????

Slowed spontaneous depolarization of SA node

A

Muscarinic

403
Q

Muscarinic AChR or Nicotinic AChR????

Coupled to heterotrimeric G protein

A

Muscarinic

404
Q

Muscarinic AChR or Nicotinic AChR????

Secretion of catecholamines from adrenal medulla

A

Nicotonic

405
Q

Muscarinic AChR or Nicotinic AChR????

Nonselective cation channel

A

Nicotinic

406
Q

Muscarinic AChR or Nicotinic AChR????

Metabotropic

A

Muscarinic

407
Q

Muscarinic AChR or Nicotinic AChR????

Presynaptic autoreceptors

A

muscarinic

408
Q

Muscarinic AChR or Nicotinic AChR????

Airway smooth muscle

A

Muscarinic

409
Q

The NMDA receptor has bindings sites for: (select 3)
a. gamma-aminobutyric acid
b. glutamate
c. propofol
d. ketamine
e. magnesium
f. calcium

A

B - glutamate
d - ketamine
e - magnesium

410
Q

The amino acid NT include ____, ____, and _____.

A

gutamate, ᵧ-aminobutyric acid (GABA), glycine

411
Q

_____ is the primary excitatory NT in the brain.

A

GLUTAMATE

412
Q

What is the main inhibitory NT in the brain?

A

GABA

413
Q

What is the primary inhibitor NT in teh spinal cord and lower brain stem?

A

GLYCINE

414
Q

____ and ____ are interconvertible through Krebs cycle (aka tricarboxylic acid cycle) intermediates.

A

Gutamate and GABA

415
Q

Are glutamate receptors inotropic or metabotropic?

A

they can be both

416
Q

What receptors are a target for ketamine?

A

NMDA

417
Q

What are the two ionotropic glutamate receptors?

A

NMDA and AMPA

418
Q

What is neuronal injury initiated by excessive glutamate receptor activity called?

A

excitotoxicity

419
Q

GABA receptors can be ionotropic and metabotropic. Which is which?

A

GABAa = ionotropic
GABAb = metabotropic

420
Q

Which receptor is a target for Benzos, propofol, etomidate, and volatiles?

A

GABAa

421
Q

Is the glycine receptor ionotropic or metabotropic?

A

ionotropic

422
Q

Is glutamate excitatory or inhibitory?

A

excitatory

423
Q

Glutamatergic synapses exist throughout the ____.

A

CNS

424
Q

What are excitatory responses to gluatmate?

A

motor neuron activation, pain pathway transmission, elevated pain sensation (hyperalgesia), memory formation, cerebral neurotoxicity

425
Q

Is GABA inhibitory or excitatory?

A

Inhibitory

426
Q

Most CNS ____ and ____ express GABA receptors; therefore, GABA receptors influence many neural circuits and functions.

A

neurons and astrocytes

427
Q

GABA neurons play a role in what?

A

arousal and attention; memory formation; anxiety; sleep; muscle tone

428
Q

Is glycine inhibitory or excitatory?

A

inhibitor

429
Q

What type of cells form inhibitory glycinergic synapses upon alpha motor neurons?

A

Renshaw

430
Q

Why myst glutamate be synthesized in the brain?

A

B/c it canNOT cross the BBB

431
Q

How is glutamate converted to GABA?

A

By glutamic acid decarboxylase

432
Q

IN one path for glutamate synthesis, _____ produced by the Krebs cycle serves as the substrate for GABA transaminase. What is the the product of transamination?

A

𝜶-ketoglutarate; glutamate

433
Q

How is glutamine converted into glutamate?

A

By glutaminase on the mitochondiral membrane

434
Q

What is the rate-limiting step in glutamate synthesis?

A

Glutaminase activity

435
Q

Where is glutamate stored until release?

A

synpatic vesicles

436
Q

______ reuptake glutamate from the synaptic cleft via glutamate transporters.

A

Glial cells (glutamate is converted into glutamine by the enzyme glutamine synthetase)

437
Q

What are teh 3 types of ionotropic glutamate receptors?

A
  1. N-methyl-D-aspartate (NMDA)
  2. 𝜶-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)
  3. Kainate
438
Q

Where are NMDA and AMPAs both prevalently located?

A

hippocampus and cerebral cortex

439
Q

Full activation of AMPA receptors requires waht?

A

binding of 2 glutamate molecules

440
Q

AMPA receptors are non-selective cation channels that are highly permeable to ___ and poorly permeable to ___.

A

Na; Ca

441
Q

AMPA are responsible for early post-synpatic membrane depolarization in response to _____ release.

A

glutamate

442
Q

What plays a key role in AMPA desnsitization?

A

Phosphorylation

443
Q

Full activation of NMDA receptors requires the binding of 2 ____, 2 _____ and a ______.

A

glutamates; glycine; depolarizing voltage change

These are safety locks on the NMDA receptor - each must be met for full activation

444
Q

NMDA receptors are non-selective cation channels that are highly permeable to ___ but permeable to ___.

A

Ca; Na

(opposite of AMPA)

445
Q

NMDAs are slower or faster gated than AMPA?

A

slower

NMDAs are slower-gating (Delayed) excitatory synaptic transmission.

446
Q

NMDA: a _____ binding site is located within the channel, this is also the binding site for ketamine.

A

phencyclidine (phenylcyclohexyl piperidine, PCP; “angel dust”)

447
Q

What are the 3 groups of metabotropic glutamate receptors?

A
  1. 1 coupled to Gq and activate phospholipase C
    2 & 3. coupled to Gi and prevent the formation of cAMP
448
Q

Metabotropic glutamate receptors are widely distributed where?

A

in the brain at post and pre synaptic locations and on glial cells

449
Q

What is long-term potentiation?

A

Ca+ influx through NMDA receptors plays a key role in many Ca- dependent processes, including the consolidation of short-term memories –> long term memories

450
Q

What is apoptosis?

A

programmed cell death

451
Q

What diseases is excitotoxicity implicated as a pathologic mechanism?

A

Huntington’s, Alzheimer’s, ALS, stroke and trauma, hyperalgesia, epilepsy

452
Q

What are the three safety locks of NMDA receptors?

A

voltage-dependence
2 glutamate bindings
2 glycine bindings

453
Q

Why do safety locks for NMDA receptors exist?

A

Hyperactivation would result in flooding of neurons by Ca2+ causing cell death

454
Q

What catalyzes the decarboxylation of glutamate to GABA?

A

Glutamic acid decarboxylase

455
Q

The amount of GABA in the CNS correlates to the amount of functional ____.

A

Glutamic acid decarboxylase (GAD)

456
Q

Where does conversion of glutamine to glutamate occur?

A

mitochondria

457
Q

What converts glutamine to glutamate?

A

glutaminase

458
Q

How is GABA formed and where?

A

By the decarboxylation of glutamate; in the cytoplasm

459
Q

T/F: GAD is not present in neurons using glutamate as a NT.

A

True

460
Q

Is GABA recylced?

A

Yes

461
Q

How are GABAa receptors activated?

A

the binding of 2 GABA molecules

462
Q

GABA_ receptors are pentameric ligand-gated Cl- channels.

A

A

463
Q

GABA _ receptors are 7-transmembrane G protein-coupled receptors.

A

B

464
Q

Activation of GABAb generates inhibitory effects in post-synaptic neurons via second messenger systes involving:
____
____
____
____

A

PLC
adenylyl cyclase
βᵞ unit opening of K+ channels
βᵞ closing of Ca2+ channels

465
Q

How is glycine formed?

A

From serine (an amino acid) in an enzyme-catalyzed reaction

466
Q

______ is a co-activator of the NMDA receptor.

A

Glycine

467
Q

Mutations of the glycine receptors are involved in rare neuro dx such as ____ or ____

A

human startle dx or hyperekplexia

468
Q

GABAa OR NMDA??????

Excitatory responses

A

NMDA

469
Q

GABAa OR NMDA??????

Flumazenil is antagonist

A

GABA

470
Q

GABAa OR NMDA??????

Propofol binding site

A

GABA

471
Q

GABAa OR NMDA??????

Benzo binding site

A

GABA

472
Q

GABAa OR NMDA??????

Inhibitory response

A

GABA

473
Q

GABAa OR NMDA??????

Mg ions block channel at resting membrane potential

A

NMDA

474
Q

GABAa OR NMDA??????

KEtamine binding site

A

NMDA

475
Q

GABAa OR NMDA??????

Glycine is a co-transmitter

A

NMDA

476
Q

What is the primary inhibitory NT in the spinal cord?

A

Glycine

477
Q

Which NT is associated w/ excitotoxicity?

A

Glutamate

478
Q

WHich GABA receptor is metabotropic?

A

b

479
Q

What 2 binding sites are located in the NMDA receptor channel (pore)?

A

Mg2+ and Ketamine/PCP

480
Q

Glutamate is converted to GABA by what type of enzymatic reaction?

A

Decarboxylation

481
Q

Which enzymes are required to degrade epinephrine to vanillylmandelic acid? (select 2)
a. catechol-O-methyltransferase
b. L-amino acid decarboxylase
c. monomaine oxidase
d. tyrosine hydroxylase

A

A and C

482
Q

What are the 5 biogenic amine NT?

A
  1. dopamine
  2. norephinephrine
  3. ephinephrine
  4. serotonin
  5. histamine
483
Q

What are all teh biogenic amine NT derived from?

A

amino acids by enzymatic hydroxylation and decarboxylation

484
Q

What 3 things are known as catecholamines?

A

dopamine, norepinephrine, epinephrine

485
Q

______ is the rate limiting step in catecholamine biosynthesis.

A

Tyrosine hydroxylase

486
Q

What 2 enzymes degrade NE and Epi?

A
  1. monoamine oxidase (MAO)
  2. catechol-O-methyltransferase (COMT)
487
Q

What is the end-product of catecholamine metabolism?

A

Vanillylmandelic acid (VMA)

488
Q

How is VMA eliminated?

A

urine

489
Q

serotonin is synthesized from ____

A

tryptophan

490
Q

What is the end product of serotonin metabolism?

A

5-hydroxyindoleacetic acid (5-HIAA)

491
Q

How is 5-HIAA eliminated?

A

urine

492
Q

Histamine is synthesized from _____

A

histidine

493
Q

What physiologic responses do biogenic animes cause?

A

central control of cardiac function, BP, and metabolism; coordination of movement; cognitive function; regulation of appetite and feeding; sleep; behavior

494
Q

Most biogenic amine NT receptors are _______ receptors. What is the exception?

A

metabotropic; ionotropic 5-HT3 serotonin receptor

495
Q

All catecholamines are synthesized from ______.

A

tyrosine

496
Q

Serotonin is synthesized from _______.

A

tryptophan

497
Q

Histamine is synthesized from _______.

A

histidine

498
Q

All biogenic amine NT are synthesized rom _______

A

amino acids

499
Q

What 2 enzymatic reactions are common in the biosynthesis of biogenic amine NT?

A

Hydroxylation and decarboxylation

500
Q

What occurs during hydroxylation?

A

An -OH group is added

501
Q

What occurs during decarboxylation?

A

A -CO2 group is removed

502
Q

If tyrosine supply is low, how can cells generate tyrosine?

A

From phenylalanine by hydroxylation

(tip: [maybe??? lol] the alternate name for tyrosine is hydroxyphenylalanine)

503
Q

Tyrosine is hydroxylated or decarboxylated by the enzyme tyrosine hydroxylase? What is formed?

A

HYDROXYLATED; L-DOPA

504
Q

What is the rate-limiting step in catecholamine synthesis?

A

Tyrosine hydroxylation to L-DOPA

505
Q

During catecholamine synthesis, tyrosine hydoxylase is subject to feedback inhibition by what?

A

Dopamine and NE

506
Q

During catecholamine synthesis, is L-DOPA hydroxylated or decarboxylated by aromatic L-amino acid decarboxylase? What is the result?

A

Decarboxylated; dopamine

507
Q

After Dopamine is formed from L-DOPA where does it go?

A

It is transported into vesicles by an H+-antiporter. If the neuron is dopaminergic, the path stops here.

508
Q

In nonadrenergic and adrenergic neurons or chromaffin cells, the path of catecholamine synthesis continues after Dopamine formation. In the storage vesicles, does hydroxylation or decarboxylation of the dopamine occur? What results?

A

Hydroxylation (by dopamine-β-hydroxylase); Norepinephrine

509
Q

During catecholamine synthesis, in adrenergic cells and neurons, norepinephrine moves out of the vesicles to where? What does it encounter?

A

cytoplasm; phenylethanolamine-N-methyltransferase (PNMT)

510
Q

PNMT catalyzes the ______ of NE to form ______.

A

methylation (CH3); epinephrine

511
Q

Put these in order for which they are created: Norepinephrine, Dopamine, and Epinehprine

A

Dopamine –> Norepinephrine –> Epinephrine

512
Q

What 2 enzymes metabolize catecholamines?

A

Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)

513
Q

____ is a mitochondrial outer-membrane enzyme found in most neurons and other tissues.

A

MAO

514
Q

What two isoforms does MAO exist in?

A

MAO-A and MAO-B

515
Q

What does MAO-A preferentially degrade?

A

Dopamine, Epi, serotonin

516
Q

what does MAO-B degrade?

A

Dopamine more rapidly than serotonin or NE

517
Q

_____ is a relatively nonspecific cytosolic enzyme found in endothelial cells, the heart, kidneys, liver, smooth muscle, and glial cells.

A

COMT

518
Q

What is the end-product of catecholamien metabolism?

A

Vanillymandelic acid

519
Q

How is pheochromocytoma diagnosis made?

A

biochemical determination of free catecholamine concentration and catecholamine metabolites (VMA) in urine

520
Q

What is the major metabolite of dopamine? How is Dopamine metabolized?

A

Homovanillic acid (HVA); MAO and COMT

521
Q

Does serotonin cross the BBB?

A

No (brain must synthesize its own)

522
Q

What is the substrate for serotonin synthesis?

A

Dietary L-tryptophan

523
Q

What is serotonin metabolized to?

A

5-hydroxyindoleacetic acid (5-HIAA)

524
Q

How is 5-HIAA excreted? What do high levels in the urine show?

A

urine; consistent w/ carcinoid tumors

525
Q

______ is an imidazole amine consisting of an imidazole ring and an amino group connected by 2 methylene groups.

A

Histamine

526
Q

How is histamine synthesized in the periphery?

A

By mast cells and basophils

527
Q

Does histamine cross the BBB?

A

No

528
Q

The brain synthesizes its own histamine from _______.

A

L-histidine (an amino acid)

529
Q

Histidine is _______ to form histamine

A

decarboxylated

530
Q

What metabolizes histamine?

A

oxidative paths in liver

531
Q

What is one major metabolite of histamine that can be measured in the urine to determine the amount of histamien that has been released systemically?

A

imidazole acetic acid

532
Q

All catecholamine NT are derived from which amino acid?

A

L-tyrosine

533
Q

What enxymatic reaction is present in ALL biogenic amine NT biosynthesis?

A

Decarboxylation

534
Q

Match each adrenergic receptor with the G protein alpha subunit coupled to the receptor: alpha 2; alpha 1; beta
& Gq, Gi, Gs

A

Alpha-2 Receptor - Gi
Alpha-1 Receptor - Gq
Beta Receptor - Gs

535
Q

How are biogenic amine NT removed from the synaptic cleft?

A

By reuptake into the presynaptic terminal or uptake into non-neuronal cells and organs

536
Q

What are the 3 main classes adrenergic receptors can be divided into?

A

Alpha-1
Alpha-2
Beta

537
Q

Derangements of serotonergic paths contribute to what?

A

Anxiety, depression, mania, schizophrenia

538
Q

What serotonin receptor is the target of antagonists for PONV and Chemo-induced N/V?

A

5-HT3

539
Q

What role do serotonergic neurons play?

A

sleep and wakefulness, emotions, cognition, and CV, respiratory, and intestional activitives

540
Q

What role do histaminergic neurons play?

A

arousal and attention, memory, learning, mood

541
Q

About ___% of the dopamine entering the terminal is recycled into vesicles by the H+-antiporter. The remaining ___% is destroyed by the mitochondrial enzyme MAO.

A

50%; 50%

542
Q

Where is the largest concentration of dopaminergic neurons in the brain?

A

the substantia nigra

543
Q

The dopaminergic neurons in the substantia nigra are crucial for what?

A

coordinating movements

544
Q

Degeneration of Dopaminergic neurons in the substantia nigra causes _______.

A

Parkinson’s disease

545
Q

Besides the substantia nigra, other dopaminergic neurons in the CNS are involved with ______ and ______.

A

motivation and reward (limbic system) and cognitive functions such as spatial learning and memory (prefrontal cortext)

546
Q

How many types of dopamine receptors are there?

A

5

547
Q

The D1-like dopamine receptors are ___ and ____. They activate what?

A

D1 and D5; PKA through adenylyl cyclase and cAMP, and PKC through PLC

548
Q

The D2-like dopamine receptors are ___, _____, and ____. They inhibit what?

A

D2, D3, and D4; inhibit adenylyl cyclase and thus reduce PKA activity which ultimately leads to decreased neuronal excitability

549
Q

What is implicated in the pathogensis of schizophrenia?

A

Overactive D2-like receptors

550
Q

Where is the major concentration of noradrenergic neurons in the CNS?

A

Locus coeruleus in the pons

551
Q

Noradrenergic neurons from the locus coeruleus reach the ___, ____, ____ and ____.

A

thalamus, hypothalamus, limbic system, and cerebral cortex

552
Q

What the noradrenergic projections important in?

A

arousal, attention (Vigilance ), and feeding behaviors

553
Q

2 major groups of adrenergic (epi) neurons have been identified in the CNS:
1. _________________
2. _________________

A
  1. Rostral ventrolateral medulla
  2. Nucleus tractus solitarius
554
Q

In the peripheral nervous system, NE is released from where?

A

from most post-ganglionic symapthetic neurons onto the target tissues

555
Q

In the peripheral nervous system, Epi is released from where?

A

chromaffin cells of the adrenal medulla into the circulation in response to stress

556
Q

All adrenergic receptors are metabotropic or ionotropic?

A

Metabotropic

557
Q

Adrenergic receptor classes are distinguished by their relative sensitivity to _____.

A

Isoproterenol (N-isopropyl-noradrenaline)

558
Q

Isoproterenol activates ____ receptors, whereas ____ receptors are poorly activated by isoproterenol.

A

Beta; alpha

559
Q

NE preferentially binds to what receptors?

A

A1, A2, and B1

560
Q

Activation of ______ results in inhibition of NE release

A

presynaptic alpha-2

561
Q

Epi is an agonist of what receptors?

A

alpha and beta

562
Q

At low concentrations Epi has predominately ____ effects, while at higher concentrations, its ___ effects become more pronounced.

A

Beta; A1

563
Q

Serotonergic neurons are clustered in several ______.

A

midline raphe nuclei

564
Q

Rostral raphe nuclei project to the ___, ___, and ____.

A

thalamus, limbic system, and cortex

565
Q

Caudal raphe nuclei project to the _______ and _____

A

spinal cord; within the brain stem

566
Q

How many of the 4 main classes of serotonin receptors are metabotropic?

A

3

567
Q

5-HT1 receptors inhibit

A

adneylyl cyclase

568
Q

5-HT2 receptors usually stimulate ___ and _____

A

stimulate PLC and mobilization of Ca2+

569
Q

5-HT4 receptors stimulate ______

A

adenylyl cylcase and pKA activation

570
Q

Activation of 5-HT3 receptors leads to rapid _____

A

membrane depolarization

571
Q

How do 5-HT3 antagonits exert their effect?

A

they block receptors in the area postrema as well as in the vagus nerve, which normally activates the vomiting center

572
Q

Where is the highest density of histamine-containing neurons found?

A

in the tuberomammillary region of the hypothalamus

573
Q

Gs, Gi, or Gq???????

5-HT4

A

Gs

574
Q

Gs, Gi, or Gq???????

Alpha-2

A

Gi

575
Q

Gs, Gi, or Gq???????

Alpha-1

A

Gq

576
Q

Gs, Gi, or Gq???????

D1

A

Gs

577
Q

Gs, Gi, or Gq???????

5-HT1

A

Gi

578
Q

Gs, Gi, or Gq???????

Beta

A

Gs

579
Q

Gs, Gi, or Gq???????

5-HT2

A

Gq

580
Q

Gs, Gi, or Gq???????

D2

A

Gi

581
Q

The largest concentration of dopaminergic neurons is in the brain is in what strucutre?

A

Substantia nigra

582
Q

What cells in the adrenal medulla release Epi into the circulation?

A

chromaffin

583
Q

Zofran targets which specific serotonin receptor?

A

5-HT3

584
Q

What is the substrate for nitric oxide synthase?
a. L-citrulline
b. Nitric oxide
c. L-arginine
d. Guanosine triphosphate

A

C

585
Q

What are the purinergic NT?

A

ATP, ADP, and adenosine

586
Q

T/F: Purinergic receptors are ionotropic.

A

False - purinergic receptors are both ionotropic and metabotropic

587
Q

ALl neuropeptides act on what receptors? and what happens?

A

metabotropic; they induce alterations in teh excitability of post-synaptic cells

588
Q

____ is a universal intercellular messenger, acting as both an autocrine and paracrine signaling molecule.

A

NO

589
Q

At body temp, NO is a small, ______ that easily permeates lipid membranes, “soaking” the surrounding tissue cell.

A

lipid-soluble gas

590
Q

What does nitric oxide synthase do?

A

converts L-arginine to L-citrulline and NO

591
Q

Many effects of NO are mediated locally by soluble guanylyl cyclase which produces ____ from GTP.

A

cGMP

592
Q

NO plays a role in central sensitization to _____

A

pain

593
Q

What roles do purine and pyrimidine nucleotides do?

A
  • precursors of DNA and RNA
  • components of enzymes
  • energy currency
  • allosteric modulators of enzymes
  • second messengers
  • auto-and paracrine first messengers
594
Q

Purine bases are _____ and ______

A

adenine (A) and guanosine (G)

595
Q

What are two examples of purines?

A

theophylline and caffeine

596
Q

Pyrimidine bases are ___, ____ and ____

A

cytosine (C), thymidine (T), and uracil (U)

597
Q

______ acid is a pyrimidine.

A

Barbituric

598
Q

What is a nucleotide composed of?

A

A 5-carbon sugar(pentose), nitrogenous base, and at least 1 phosphate group

599
Q

ATP, ADP and AMP and GTP, GDP, and GMP are pyrimidine or purine nucleotides?

A

Purine

600
Q

UTP, UDP, and UMP and CTP, CDP, CMP are pyrimidine or purine nucleotides?

A

Pyrimidine

601
Q

What is a nucleoside composed of?

A

A pentose and a nitrogenous base, with NO phosphate groups

(the phosphate groups differentiate a nucleoside and nucleotide)

602
Q

What are the main purinergic transmitters?

A

ATP, ADP, and adenosine

603
Q

What purinergic transmitter is frequently coreleased with other transmitters?

A

ATP

604
Q

Adenosine is generated from ___ in the extracellular space (ex: synaptic cleft) by an enzyme, _____.

A

ATP; ectonucleotidase

605
Q

Adenosine plays a role in the _____ state.

A

sleep/wake

606
Q

Increased or decreased adenosine levels promote sleep?

A

Increased

607
Q

Increased or decreased adenosine promotes wakefulness?

A

Decreased

608
Q

Adenosine plays a crucial role in protecting tissues from damage. A strong ___ in adenosine levels. in the ECF is an emergency signal indicating an acute oxygen deficiency (CVA, angina, MI)

A

INCREASE

609
Q

What dysrhythmia is adenosine indicated for? What does it do?

A

SVT; it stops the heart briefly to allow the SA node to assume the role of the dominant pacemaker

610
Q

What are purinergic NT metabolized to?

A

5’-AMP

611
Q

What are the two families of purinergic receptors?

A

P1 and P2

612
Q

Are P1 and P2Y receptors metabotropic or ionotropic?

A

Metabotropic

613
Q

Is P2X metabotropic or ionotropic?

A

Ionotropic

614
Q

What role do P2X receptors play on sensory nerves?

A

Detect and signal tissue damage and inflammation

615
Q

Some ____ receptors are found on the presynaptic membrane and serve to suppress ATP release by negative feedback through Gi paths.

A

P2Y

616
Q

PLT aggregation is induced by ADP binding to _____ receptors.

A

P2Y

617
Q

How does NO arise?

A

From the oxidation. of the guanidino group of L-arginine

618
Q

What does generation of NO require?

A

NADPH, molecular oxygen, and is catalyzed by a family of oxygenases known as NO synthases

619
Q

How many families of nitric oxide synthase are there?

A

3

620
Q

What families of nitric oxide synthase are calcium-dependent enzymes?

A

NOS1 and NOS3

621
Q

NO is both an ____ messenger and a ____ gas.

A

endogenous; cytotoxic

622
Q

NO effects depend on what?

A

Its tissue concentration

623
Q

At low concentrations, what does NO function as?

A

A signaling molecule and interacts w/ a cytoplasmic receptor, soluble guanylyl cyclase (sGC)

624
Q

At high concentrations, NO exhibits what effects?

A

Signaling effects by modifying proteins by nonenzymatic S-ntirosylation

625
Q

At extremely high concentrations of NO, what dominates?

A

the cytotoxic effects … overstimulation of NO formation plays a role in life-threatening evens such as CVA and endotoxin shock

626
Q

The _____ complex activates NOS.

A

Ca2+-calmodulin

627
Q

Activation of NOS results in the formation of ___ and ___ from L-arginine.

A

NO and citrulline

628
Q

NO interacts with the heme moiety of ______ (sGC).

A

soluble guanylate cyclase

629
Q

sGC activated by NO catalyzes the conversion of ___ to ____ in teh post-synaptic neuron.

A

GTP –> cGMP

630
Q

Retrograde diffusion of NO into the pre-synatpic terminal has a ____ feedback effect.

A

positive

631
Q

NO is a highly reactive free radical wiht a half-life of how long?

A

a few seconds

632
Q

When are functions of NO terminated?

A

When NO is converted to nitrities and nitrates by oxygen and water

633
Q

What roles do NO play?

A

sleep, controls normal feeding behavior, role in GI function

634
Q

What is long-term potentiation?

A

An activity-dependent increase in synaptic efficacy

635
Q

What is long-term depression?

A

A decrease in synpatic efficacy due to prolonged “weak” stimulation of a synapse

636
Q

NO is synthesized and released by endothelial cells and thus has an important role in the control of ______.

A

vascular tone

637
Q

Are GTP and ATP classified as purines or pyrimidines?

A

Purines

638
Q

What enzyme converts ATP to adenosine in the synaptic cleft?

A

Ectonucleotidase

639
Q

Are all neuropeptide receptors ionotropic or metabotropic?

A

Metabotropic

640
Q

What signaling complex activates nNOS?

A

Ca2+/CaM (calmodulin)

641
Q

An activity-dependent increase. in synaptic efficacy is called:

A

Long-term potentiation (LTP)

642
Q

What cytosolic heme- containing enzyme is activated by NO?

A

Soluble guanylyl cyclase (sCG)

643
Q

The receptor for insulin is a:
a. receptor guanylylcyclase
b. receptor tyrosine kinase
c. tyrosine kinase-associated receptor
d. receptor serine/threonine kinase

A

B

644
Q

What are the 5 major categories of enzyme-linked receptors?

A
  1. receptor guanylylcyclase
  2. receptor tyrosine kinases
  3. tyrosine kinase-associted receptors
  4. receptor serine/threonine kinases
  5. receptor tyrosine phosphates
645
Q

Receptor _____ convert GTP to cGMP.

A

guanylyl cyclases

646
Q

What is the largest family of enzyme-linked receptors?

A

Receptor tyrosine kinases

647
Q

____ and ____ are ligands to RTKs.

A

Insulin and growth factors

648
Q

Mutations. in________ are associated with. a wide variety of cancers.

A

receptor tyrosine kinases (RTK)

649
Q

T/F: Tyrosine kinase associated receptors do not have intrinsic enzyme activity.

A

True

650
Q

Receptor _____ are important mediators of cell growth and differentiation.

A

serine-threonine kinase

651
Q

Transmembrane catalytic receptors are also known as ______ receptors

A

enzyme-linked

652
Q

What do transmembrane catalytic receptors do?

A

transduce an extracellular ligand-binding interaction into an intracellular effect by activating a “linked” enzymatic domain

653
Q

Enzyme-Linked Receptors:
________ contain a cytosolic domain that catalyzes the formation of cGMP from GTP.

A

Receptor Guanylyl Cyclases

654
Q

Enzyme-Linked Receptors:
______ are the largest group to transmembrane catalytic receptors.

A

Receptor Tyrosine Kinases

655
Q

Enzyme-Linked Receptors:
________ lack inherent catalytic activity. These receptors recruit active cytosolic signaling proteins in a ligand-dependent manner.

A

Tyrosine Kinase Associated receptors

656
Q

Enzyme-Linked Receptors:
______ have intrinisic catalytic activity and phosphorylate serine and threonine residues on target cytosolic proteins.

A

Receptor serin/threonine kinases

657
Q

Enzyme-Linked Receptors:
_______ dephosphorylate tyrosine residues on other transmembrane receptors or on cytosolic proteins. They play important roles in cells of the immune system.

A

Receptor Tyrosine Pohsphates

658
Q

Transmembrane catalytic receptors are ____ membrane-spanning proteins.

A

single

659
Q

What are. theligands for enzyme-linked receptors?

A

Polypeptides and larger proteins

660
Q

____ catalyzes teh metabolism of cGMP to 5’-GMP, terminating the actino. ofcGMP.

A

PDE5

661
Q

____, ____, and ____ are ligands for receptor guanylyl cyclases.

A

ANP, BNP, and CNP

662
Q

_______, a recombinant version of native natriuretic peptides, is used in the treatment of decompnesated HF.

A

Nesiritide

663
Q

T/F: RTKs always work in pairs.

A

True

664
Q

What tissues express higher levels of the insuline receptor?

A

energy-storing tissues of liver, muscle, and adipocytes

665
Q

Obese people have varying degrees of _____ resistance.

A

leptin

666
Q

Receptor Guanylyl Cyclases, receptor tyrosine kinases, tyrosine kinase-associated receptors, or serine-threonine kinase receptors????

Tyrosine kinase activity is built-in to the receptor

A

Receptor tyrosine kinases

667
Q

Receptor Guanylyl Cyclases, receptor tyrosine kinases, tyrosine kinase-associated receptors, or serine-threonine kinase receptors????

Insulin receptor

A

Receptor tyrosine kinases

668
Q

Receptor Guanylyl Cyclases, receptor tyrosine kinases, tyrosine kinase-associated receptors, or serine-threonine kinase receptors????

ANP is a ligand

A

Receptor guanylyl cyclases

669
Q

Receptor Guanylyl Cyclases, receptor tyrosine kinases, tyrosine kinase-associated receptors, or serine-threonine kinase receptors????

Cell differntiation

A

serine-threonin kinase receptors

670
Q

Receptor Guanylyl Cyclases, receptor tyrosine kinases, tyrosine kinase-associated receptors, or serine-threonine kinase receptors????

TGF-β is a ligand

A

Serine-threonin kinase receptors

671
Q

Receptor Guanylyl Cyclases, receptor tyrosine kinases, tyrosine kinase-associated receptors, or serine-threonine kinase receptors????

JAK-STAT system is downstream target

A

Tyrosine kinase-associated receptors

672
Q

Receptor Guanylyl Cyclases, receptor tyrosine kinases, tyrosine kinase-associated receptors, or serine-threonine kinase receptors????

Lepitn receptor

A

Tyrosine kinase-associated receptors

673
Q

Receptor Guanylyl Cyclases, receptor tyrosine kinases, tyrosine kinase-associated receptors, or serine-threonine kinase receptors????

GTP to cGMP

A

Receptor guanylyl cyclases

674
Q

Which signaling molecules bind to nuclear receptors (Select 3)?
a. Ach
b. Testosterone
c. Vit D
d. Erythropoietin
e. Triiodothyronine
f. Gamma-aminobutyric acid

A

B, C, E

675
Q

Most chemical signals bind. to receptors where?

A

transmembrane

676
Q

________ complexes are activated transcription factors that regulate the expression of target genes in the DNA.

A

Ligated (ligand-bound) nuclear receptor complexes

677
Q

The intracellular receptor family includes receptors for ____,____,___,___, and ____.

A

steroid hormones
prostaglandins
Vit d
thyroid hormones
retinoic acid

678
Q

_______ are activated transcription factors that bind. in a highly specific manner. to short DNA sequences called hormone response elements.

A

Ligand-bound nuclear receptors

679
Q

_______ increase basal metabolic rate by stimulating futile cycles of catabolism and anabolism.

A

Thyroid hormones

680
Q

What are. the2 subfamilies of nuclear receptors?

A
  1. receptors for steroid hormones
  2. receptors for retinoic acid, thyroid hormone, and Vit D
681
Q

Steroid hormone receptors are ______

A

homodimers (e.g., PR-PR for progesterone)

682
Q

Receptors for retinoic acid, thyroid hormones, and Vit D form heterodimers with the _______ receptor (RXR).

A

retinoic acid receptor

683
Q

Preferred Ligand: 17β-estradiol

Receptor/Transcription Factor: _______

A

Estrogen Receptor

684
Q

Preferred Ligand: Progesterone

Receptor/Transcription Factor: _______

A

Progesterone Receptor

685
Q

Preferred Ligand: Testosterone

Receptor/Transcription Factor: _______

A

Androgen Receptor

686
Q

Preferred Ligand: Cortisol

Receptor/Transcription Factor: _______

A

Glucocorticoid Receptor

687
Q

Preferred Ligand: Aldosterone

Receptor/Transcription Factor: _______

A

Mineralocorticoid receptor

688
Q

Preferred Ligand: All-trans-retinoic acid

Receptor/Transcription Factor: _______

A

Retionic acid receptor

689
Q

Preferred Ligand: 9-cis-retinoic acid

Receptor/Transcription Factor: _______

A

Retinoid X Receptor

690
Q

Preferred Ligand: Triiodothyroinine (T3)

Receptor/Transcription Factor: _______

A

Thyroid hormone receptor

691
Q

Preferred Ligand: 1,25-dihydroxycholecalciferol (D3)

Receptor/Transcription Factor: _______

A

Vitamin D Receptor

692
Q

____, ____, and _____ receptors are mainly solbule cytoplasmic receptors.

A

Glycocorticoid, mineralocorticoid, and androgen

693
Q

_____ and ____ are primarily soluble nuclear receptors.

A

Estrogen and progesterone

694
Q

INtracellular receptors are also called ____ receptors

A

Nuclear

695
Q

What nuclear receptors are bound. to DNA in the nucleus?

A

Retinoic acid, thyroid, and Vit D

696
Q

_____ nuclear receptors are frequently complexed to chaperone (“heat shock”) proteins.

A

Cytoplasmic

697
Q

T/F: Thyroid hormones have effects. onvirtually every cell in the body.

A

True

698
Q

Free thyroid hormone, T3 and T4, enters the cell how?

A

Through passive diffusion and active transport

699
Q

In the cell, T4 is usually converted to ____ by a ____.

A

T3; deiodinase

700
Q

Does the thyroid receptor in the nucleus have a greater affinity for T3 or T4?

A

T3 (10x greater affinity)

701
Q

T3 is responsible for ___% of the occupancy. of thyroid receptors in the euthyroid state.

A

90

702
Q

Ligand-bound ____ complexes bind to thyroid response elements on DNA and act as transcription activators or repressors in a tissue-specific fashion.

A

TR-RXR

703
Q

How do thyroid hormones increase basal metabolic rate?

A

By stimulating futile cycles of both catbolism and anabolism

704
Q

What stage of life are thyroid hormones essential for normal human development?

A

Infancy

705
Q

What causes congenital hypothyroidism?

A

Congenital deficiency of iodine and thus thyroid hormone during infancy

706
Q

If hypothyroidism is recognized and corrected within _____ after birth, then development - including mental development. -can proceed almost normally.

A

7 -14 days

707
Q

THe DNA-binding site for ligand-bound nuclear receptors. iscalled an:

A

Hormone response element

708
Q

An unoccupied cytoplasmic intracellular receptor is frequently complexed to a/n:

A

Chaperone protein (heat shock protein)

709
Q

An unoccupied cytoplasmic intracellular receptor is frequently complexed to a/n:

A

Chaperone protein (heat shock protein)

710
Q

WHat syndrome is associated with congenital hypothyroidism?

A

Cretinism

711
Q

Which statement is NOT a feature of cell death by apoptosis?
a. apoptosis is genetically programmed
b. cells shrink during apoptosis
c. plasma membranes are intact during apoptosis
d. inflammation in surrounding tissues is common during apoptosis

A

D

712
Q

What happens during necrosis of the cell:
Cells swell or shrinks??
What happens to DNA?
What happens to plasma membranes?
What happens to cell contents?
What happens to adjacent tissues?

A

Cell swells
DNA condenses and dissolves
Membranes are disrupted
Contents dissolve and leak out
Adjacent tissues undergo inflammatory process

713
Q

What is necrosis of the cell?

A

Cell death. by uncontrolled chaotic cellular events in response to cell injury

714
Q

What. is apoptosis of the celll?

A

Genetically controlled and programmed cell death pathways

715
Q

What happens during apoptosis of the cell:
Cells swell or shrinks??
What happens to DNA?
What happens to plasma membranes?
What happens to cell contents?
What happens to adjacent tissues?

A

-Cells shrink
-Nucleus is fragmented
-Membranes are intact
-Contents are usually intact & components are packaged into”bite-sized” apoptosomes and digested by phagocytosis
-No inflammation occurs in surrounding tissues

716
Q

T/F: Apoptosis death is normal.

A

True

717
Q

What 2 paths initiate apoptosis?

A
  1. intrinsic - mitochondrial path
  2. extrinsic - death receptor-initiated path
718
Q

During apoptosis, the intrinsic and extrinsic paths converge on. the____ pathway.

A

Effector (executioner)

719
Q

What drugs cause apoptosis?

A

Almost all chemo drugs cause apoptosis of cancer cells

720
Q

Excessive levels of ____ lead to neuronal injury or neuronal death by apoptosis.

A

Ca2+

721
Q

What are the 3 forms of cell death?

A

Necrosis, apoptosis, and autophagic

722
Q

When does autophagic death occur?

A

If apoptosis is blocked or defective

723
Q

Cell death: Necrosis or Apoptosis???

Process is uncontrolled

A

Necrosis

724
Q

Cell death: Necrosis or Apoptosis???

Process is genetically programmed

A

Apoptosis

725
Q

Cell death: Necrosis or Apoptosis???

Cell enlarges and swells

A

Necrosis

726
Q

Cell death: Necrosis or Apoptosis???

Cell is reduced and shrinks

A

Apoptosis

727
Q

Cell death: Necrosis or Apoptosis???

Nucleus pyknosis –> karyolysis

A

Necrosis

728
Q

Cell death: Necrosis or Apoptosis???

Nucleus fragmentation into nucleosome sized fragments

A

Apoptosis

729
Q

Cell death: Necrosis or Apoptosis???

Plasma membrane is disrupted

A

Necrosis

730
Q

Cell death: Necrosis or Apoptosis???

Plasma membrane is intact; yet altered structure can occur (especially orientation of lipids)

A

Apoptosis

731
Q

Cell death: Necrosis or Apoptosis???

Cell contents undergo enzymatic digestion and may leak out of cell

A

Necrosis

732
Q

Cell death: Necrosis or Apoptosis???

Cell contents are intact. andmay be released in apoptotic bodies

A

Apoptosis

733
Q

Cell death: Necrosis or Apoptosis???

Adjacent inflammation frequently occurs

A

Necrosis

734
Q

Cell death: Necrosis or Apoptosis???

Adjacent inflammation does not occur

A

Apoptosis

735
Q

In adults, billions of cells die each hour. in tissues such as the ___ and ____ and are replaced by new cells.

A

Intestine and bone marrow

736
Q

The programmed destruction. ofcells during ____ is crucial to normal growth and development.

A

Embryogenesis

737
Q

DNA damage by _____, ____, and ______ will stimulate apoptosis if the insult is mild. Larger does of the same stimuli may lead to necrosis.

A

radiation, cytotoxic anticancer drugs, hypoxia

738
Q

What 3 neurodegenerative diseases cause accumulation. of misfolded proteins that lead to apoptosis?

A

Alzheimer’s, Huntington’s and Parkinson’s

739
Q

What are the main biochemical features of apoptosis?

A
  1. activation. of caspases
  2. cell components break into fragments
  3. membrane alteration. and recognition by phagocytes
740
Q

What 2 families of proteins are key regulators of apoptosis?

A

Caspases and B-cell lymphoma proteins

741
Q

What are the initiator caspases?

A

CAS-2, -8,-9, -10

742
Q

What happens after initiator caspases are activated?

A

Initiator caspases dimerize and undergo proteolytic cleavage from a procaspase to the active caspase

743
Q

What are the effector (executioner) caspases?

A

CAS-3, -7

744
Q

How are effector caspases activated?

A

By the proteolytic attack of initiator caspases

745
Q

What. isthe major mechanism of apoptosis in all mammalian cells?

A

The mitochondiral pathway

746
Q

Apoptosis (Mitochondrial Path): Damage to mitochondria by ____ or ____ result. in the opening of large pores (called ____ channels) in the mitochondrial inner membrane.

A

reactive oxygen species (ROS); increases. in intracellular Ca2+; Bax/Bak channels

747
Q

Apoptosis (Mitochondrial Path): What resides in the cytoplasm and mitochondrial membranes that keeps Bax/Bak in check in normal healthy cells?

A

Bcl-2

748
Q

Apoptosis (Mitochondrial Path): After the mitochondria is damaged and pores are opened, what happens?

A

Cytochrome C and other proteins leak through the channels; mitochondria swell and may rupture

749
Q

Apoptosis (Mitochondrial Path): The _____ activates caspase-9 and commits the cell to apoptosis.

A

apoptosome

750
Q

Apoptosis (Death Receptor-Initiated): Extracellular signals bind to. a________ receptor.

A

trimeric transmembrane death receptor

751
Q

Apoptosis (Death Receptor-Initiated): The cytosolic portion of the death receptor has a death domain that recruits what?

A

Several molecules of procaspase-8

752
Q

Apoptosis (Death Receptor-Initiated): The recruited procaspase-8 aggregate undergoes autoproteolytic cleavage releasing ______.

A

active caspase-8

753
Q

Apoptosis (Executioner [death] Path):
Caspase-9 from. the____ path and caspase-8 from the ____ path converge upon executioner caspases __ and ___.

A

intrinsic; extrinsic; -3 and -7

754
Q

What do executioner caspases do?

A

They are proteolytic enzymes that degrade cellular components - especially. the nucleus- into small fragments

755
Q

What engulfs and processed apoptotic bodies?

A

Phagocytes

756
Q

How quickly does phagocytosis of apoptoic cells occur?

A

Within minutes (so it does it w/o leaving a trace and w/o causing inflammation)

757
Q

What. is signal for phagocytes to engulf the cells during apoptosis?

A

The phosphatidylserine phospholipid that is flipped to the outer leaflet of the membrane by caspases

758
Q

Which protein keeps mitochondrial Bax/Bak pores in check. in healthy cells?

A

Bcl-2

759
Q

Do most chemo durgs cause necrosis or apoptosis?

A

Apoptosis

760
Q

What type. of cell digests apoptotic bodies?

A

Phagocytes

761
Q

Intrinsic Apoptic pathway OR extrinsic apoptotic pathway OR execution apoptotic pathway???

Apoptosome activates caspase-9

A

Intrinsic

762
Q

Intrinsic Apoptic pathway OR extrinsic apoptotic pathway OR execution apoptotic pathway???

Death pathway

A

Execution

763
Q

Intrinsic Apoptic pathway OR extrinsic apoptotic pathway OR execution apoptotic pathway???

Caspase-8

A

Extrinsic

764
Q

Intrinsic Apoptotic pathway OR extrinsic apoptotic pathway OR execution apoptotic pathway???

Cell components. are packed into bite-sized apoptotic bodies

A

Execution

765
Q

Intrinsic Apoptotic pathway OR extrinsic apoptotic pathway OR execution apoptotic pathway???

Mitochondria initiate

A

Intrinsic

766
Q

Intrinsic Apoptotic pathway OR extrinsic apoptotic pathway OR execution apoptotic pathway???

Death Receptors initiate

A

Extrinsic

767
Q

Intrinsic Apoptotic pathway OR extrinsic apoptotic pathway OR execution apoptotic pathway???

Caspase-3 and Caspase-7

A

Execution

768
Q

Intrinsic Apoptotic pathway OR extrinsic apoptotic pathway OR execution apoptotic pathway???

Bax/Bak channel

A

Intrinsic

769
Q

In the presynaptic nerve terminal, opioid-activated G protein βᵞ subunits block:
a. voltage-gated Ca2+ channels
b. voltage-gated Na channels
c. voltage-gated K+ channels
d. voltage-gated Cl- channels

A

A - Ca2+ channels

770
Q

B1 adrenoreceptor stimulation of cardiac myocytes produces positive chronotropic, dromotropic, inotropic, and lustiropic effects by ____ mediated signal transduction paths.

A

cAMP

771
Q

Many signals. at endothelial cells lead to the production of ____ and ___

A

NO and vasodilation

772
Q

Opioids exert _____ synaptic inhibitory responses in neurons through _____ receptor signal transduction paths.

A

pre and post; G protein-coupled

773
Q

What plays a key role. inwater regulation at the terminal nephron?

A

Vasopressin (Arginine Vasopressin [AVP]) and ADH

774
Q

What. is the sole enzyme for terminating cyclic nucleotide signals?

A

Cyclic nucleotide phosphodiesterases (PDE)

775
Q

Positive inotropy = ____

A

contractility

776
Q

Positive lusitropy = ______

A

relaxation

777
Q

Positive chronotropy = _____

A

HR

778
Q

Positive dromotropy = ______

A

conduction velocity

779
Q

Stimulation of B1 G protein-coupled receptors on cardiac myocytes activates ____ and increases intracellular ___.

A

adenylyl cyclase; cAMP

780
Q

After B1 stimulation, High levels of cAMP activate ____

A

protein kinase A (PKA)

781
Q

The medications, ___, ___, ___ and ____ donate NO directly to vascular smooth muscle cells, leading to relaxation and vasodilations.

A

Nitroglycerin, sodium nitroprusside, and isosorbide dinitrate

782
Q

What are the 4 families of opioid receptors?

A
  1. Mu
  2. Delta
  3. Kappa
  4. Nocicpetin
783
Q

Opioids: In ___synpatic neurons, Gβᵞ subunits block voltage-gated Ca2+ channels.

A

Pre

784
Q

Vasopressin plays a role in BP control at what 2 tissues?

A

Blood vessels and nephrons

785
Q

Vasopressin binds to ____ receptors on the basolateral membrane, activating the heterotrimeric G_ protein.

A

g protein-coupled V2; S

786
Q

PKA activation from Vasopressin does what?

A

Phosphorylates the water channel aquaporin 2 and activates transport. and fusion (exocytosis) of aquaporin-containing vesicles into the apical membrane

787
Q

Vasopressin: Increased APQ2 in the apical membrane _____ water reabsorption.

A

Increases

788
Q

Vasopressin binds to ___ receptors on vascular smooth muscle.

A

V1

789
Q

What. is a phosphodiesterase?

A

A hydrolase that breaks a phophodiester bond

790
Q

When does a phosphodiester bond happen?

A

When 2 hydroxyl groups of phosphoric acid (H3PO4) react w/ 2 hydroxyl groups attached to carbons to form 2 ester bonds

791
Q

______ form the backbone of DNA and RNA.

A

Phosphodiester bonds

792
Q

How many families of phosphodiesterases are there?

A

11

793
Q

PDE__ is nonselective for cAMP and cGMP, but binds to cAMP w/ 10x the affinity of cGMP binding.

A

3

794
Q

Where is PDE3 found?

A

Heart, vascular and placental smooth muscle, and tissues important in energy homeostasis (liver, pancreatic beta cells, adipocytes)

795
Q

Name 2 selective PDE3 inhibitors.

A

Milrinone and (in)amrinone

796
Q

T/F: 2nd messengers are tissue specific.

A

True

797
Q

PDE3 inhibitors ___ cAMP levels

A

increase

798
Q

What are the outcomes of PDE3 inhibitors?

A

Positive chronotropy, dromotropy, inotropy, and lustiropy & vasodilation

799
Q

What is Milrinone used for?

A

PHTN, cerebral vasospasm after aneurysmal subarachnoid hemorrhage, neonatal septic shock

800
Q

How is milrinone eliminated?

A

REnal excretion

801
Q

PDE__ is cGMP selective.

A

PDE5

802
Q

Where is PDE5 found? Where. isthe highest concentration?

A

tissues throughout the body;
Corpus cavernosus (penis & clitoris), vascular smooth muscle, and PLT

803
Q

Name 3 PDE5 inhibitors.

A

Sildenafil, Vardenafil, Tadalafil

804
Q

What are PDE5 inhibitors used for?

A

Erectile dysfunction, PHTN, high-altitude sickness, memory dysfunction

805
Q

How are PDE5 inhibitors metabolzied?

A

by CYP450 in liver

806
Q

PDE__ is cAMP selective.

A

4

807
Q

What does PDE4 do?

A

MOdulates B2-adrenergic responses in pulmonary smooth muscle

808
Q

Name 1 PDE4 med. What is it used for?

A

Roflumilast; COPD

809
Q

What are weak, nonselective inhibitors of PDE?

A

Methylxanthines (caffeine and theopylline)

810
Q

PDE3, PDE4, or PDE5???

Nonselective for cAMP and cGMP

A

3

811
Q

PDE3, PDE4, or PDE5???

cAMP selective

A

4

812
Q

PDE3, PDE4, or PDE5???

Milrinone is. aninhibitor

A

3

813
Q

PDE3, PDE4, or PDE5???

Inhibitors. are metabolized by CYP450 3A4

A

5

814
Q

PDE3, PDE4, or PDE5???

Sildenafil is an inhibitor

A

5

815
Q

PDE3, PDE4, or PDE5???

cGMP selective

A

5

816
Q

PDE3, PDE4, or PDE5???

Inhibitors are called inodilators

A

3

817
Q

PDE3, PDE4, or PDE5???

Roflumilast is an inhbiitor

A

4

818
Q

PDE3, PDE4, or PDE5???

Modulates B2 responses in pulmonary smooth muscle

A

4

819
Q

Inhibition. of SRCA2 is relieved. by phosphorylation of?

A

Phospholamban

820
Q

Endothelial nitric oxide synthase (eNOS) is activated by?

A

Ca2+CaM complex

821
Q

Water reabsorption in principal cells of the collecting duct is increased by the insertion of what protein into the apical membrane?

A

Aquaporin 2 (APQ2)

822
Q

What are the synonyms for Vasopressin?

A
  • arginine vasopressin (AVP)
  • antidiuretic hormone (ADH)
823
Q

Which is NOT a division of the ANS?
A. sympathetic
B. somatic
C. parasympathetic
D. enteric

A

B

824
Q

The visceral nervous system is synonymous with. the ____ nervous system.

A

autonomic

825
Q

What. arethe 3 divisions of the ANS?

A

sympathetic nervous system, parasympathetic nervous system, and enteric nervous system

826
Q

Where does the ANS proide neural control to?Where does it not?

A

All parts of the body except skeletal muscle

827
Q

____ nervous system is a major player. in homeostasis.

A

Autonomic

828
Q

Central nervous system = ____ + _____

A

brain + spinal cord

829
Q

Peripheral nervous system = ___ + ____

A

12 pairs of CN + 31 pairs. of spinal nerves

830
Q

Voluntary control of skeletal muscle is the _____

A

somatic

831
Q

Involuntary control of glands and smooth muscle is the ____

A

autonomic

832
Q

Why is CN2 part of the CNS structuarlly?

A

It is covered in 3 meningeal layers

833
Q

What do somatic nervers innervate?

A

Musculoskeletal strucutres and sensory organs of the skin

834
Q

What do autonomic nerves innervate?

A

Smooth muscle, cardiac muscle, and glands

835
Q

____ results in the absence of autonomic tone to a particular organ.

A

Denervation

836
Q

Which anatomic part of the nervous system is surrounded and covered by the meninges?

A

CNS

837
Q

Which type of muscle does NOT receive ANS signals?

A

Skeletal muscle

838
Q

Sympathetic or Parasympathetic???

Miosis

A

Parasympathetic

839
Q

Sympathetic or Parasympathetic???

Mass Discharge

A

Sympathetic

840
Q

Sympathetic or Parasympathetic???

Artery tone

A

Sympathetic

841
Q

Sympathetic or Parasympathetic???

Accommodation. inthe eye

A

Parasympathetic

842
Q

What are the 3 forms extracellular signals take?

A
  1. chemical
  2. electrical
  3. mechanical
843
Q

What are thh 3 major categories of membrane-bound receptors?

A
  1. Ion channels
  2. G protein-coupled receptors
  3. Enzyme-linked receptors
844
Q

Where are intracellular receptors located?

A

The cytoplasm or nucleoplasm

845
Q

____ is. theprocess by whihc a cell converts this extracellular signal into an intracellular response.

A

Signal transduction

846
Q

T/F: An ion channel is open or closed.

A

True

847
Q

What. are the 2 ways in which a GPCR can work?

A
  1. opening or closing an ion channel
  2. activating or inhibiting enzyme inside the cell
848
Q

When an enzyme-linked receptor is at rest, the catalytic domain is inactive. oractive?

A

Inactive

849
Q

The insulin receptor in skeletal muscle being linked to an enzyme called tyrosine kinase is an example. of ______ receptors.

A

enzyme-linked

850
Q

Steroids bind to receptors in the ____. Ths is an example of ____ receptors.

A

cytoplasm; intracellular

851
Q

Thyroid hormones bind to receptors in the ____. Ths is an example of ____ receptors.

A

nucleus; intracellular

852
Q

Ion channel, GPCR, Enzyme-linked, or Intracellular?????

B1 Receptor

A

GPCR

853
Q

Ion channel, GPCR, Enzyme-linked, or Intracellular?????

Alpha or beta-gamma subunit opens or closes an ion channel

A

GPCR

854
Q

Ion channel, GPCR, Enzyme-linked, or Intracellular?????

Thyroid hormone receptor

A

Intracellular

855
Q

Ion channel, GPCR, Enzyme-linked, or Intracellular?????

Signal diffuses through membrane

A

Intracellular

856
Q

Ion channel, GPCR, Enzyme-linked, or Intracellular?????

Ligand binding to receptor activates catalytic domain

A

Enzyme

857
Q

Ion channel, GPCR, Enzyme-linked, or Intracellular?????

Substance flows along concentration gradient

A

Ion channel

858
Q

Ion channel, GPCR, Enzyme-linked, or Intracellular?????

Located in cytoplasm of nucleoplasm

A

Intracellular

859
Q

Ion channel, GPCR, Enzyme-linked, or Intracellular?????

Voltage gated potassium channel

A

Ion channel

860
Q

Ion channel, GPCR, Enzyme-linked, or Intracellular?????

Insulin receptor

A

Enzyme linked

861
Q

Ion channel, GPCR, Enzyme-linked, or Intracellular?????

Channel opens or closes

A

ion channels

862
Q

Ion channel, GPCR, Enzyme-linked, or Intracellular?????

Activates or inhibits an intracellular enzyme

A

GPCR

863
Q

Which is NOT a second messenger?
a. calcium
b. cyclic adenosine monophosphate
c. inositol triphosphate
d. glutamate

A

D

864
Q

Name the signaling sequence of GPCRs:

A

1st messenger (ligand) –> GPCR –> Effector –> 2nd messenger –> cellular response

865
Q

What 3 subunits are. inteh G protein component of GPCR?

A

alpha, beta, gamma

866
Q

What activates. theG protein?

A

The ligand-receptor interaction

867
Q

What is the function of an effector?

A

To activate or inhibit second messengers

868
Q

The intracellular response to second messengers is ___ specific.

A

Tissue

869
Q

Name 5 2nd messengers.

A
  1. cAMP
  2. cGMP
  3. Inositol triphosphate (IP3)
  4. Diacylgylcerol (DAG)
  5. Calcium Ion (CA2+)
870
Q

An example. of an endogenous ligand is a ____ or _____.

A

NT or hormone

871
Q

A _____ binds to the GPCR.

A

Ligand

872
Q

Where does the receptor portion of the GPRC lie?

A

Outside the cell membrane

873
Q

Where does the G protein reside?

A

Inside the cell membrane

874
Q

What types of G-proteins turn on effectors?

A

Gs and Gq (these are stimulatory)

875
Q

What types of G-proteins turn off an effectors?

A

Gi

876
Q

What activates. a G-protein?

A

The ligand-receptor interaction

877
Q

What happens when the G-protein is activated?

A

The alpha subunit dissociates from the beta and gamma subunits

878
Q

When does the alpha subunit rejoin the beta and gamma subunits of a G-protein?

A

When the ligand unbinds from the receptor

879
Q

What is the purpose of the effector of GPCR?

A

To produce or activate the 2nd messenger

880
Q

Enzymatic effectors (that activate/produce the 2nd messenger) include _____ and _______.

A

adenylate cyclase and phospholipase C

881
Q

Ion channel effectors (that activate the 2nd messenger) include _____ and ________, at the _____.

A

GABA-a receptors and M2 receptors. at the SA node

882
Q

What process allows a single molecule to initiate a process that activates a large number of physiologic changes - each step progressively increasing the magnitude of response? What system allows for this process?

A

Signal amplification; Second messenger system

883
Q

The second messenger modulates a network of enzymatic activity, including ____ and ____.

A

phosphatases and protein kinases

884
Q

Which component of the GPCR signaling sequence allows for amplification?

A

second messenger

885
Q

Stimulation of which receptors increases phospholipase C activity? (select 2)
a. Alpha 1
b. vasopressin 1
c. beta-1
d. muscarinic 2

A

A and B

886
Q

Gs alpha subunits stimulate what?

A

adenylate cyclase

887
Q

What does Gs alpha stimulation promote?

A

Increased cAMP levels

888
Q

Gi alpha subunits inhibit what?

A

Adenylate cyclase

889
Q

What does Gi inhibition result in?

A

decreased cAMP levels

890
Q

Gq alpha subunits activate what? And what does this cause?

A

Phospholipase C; increased IP3, DAG, and Ca2+

891
Q

Gq –> Increased ________ effector

A

Phospholipase C

892
Q

Gi –> Decreased ________ effector

A

Adenylate Cyclase

893
Q

Gs –> Increased ________ effector

A

Adenylate Cyclase

894
Q

Gs - second messenger??

A

increased cAMP

895
Q

Gi - second messenger??

A

Decreased cAMP

896
Q

Gq - second messenger??

A

Increased IP3, DAG, Ca2+

897
Q

What is the signal transduction of Alpha 1? (Gq, Gi, or Gs??)

A

Gq

898
Q

What is the signal transduction of Alpha 2? (Gq, Gi, or Gs??)

A

Gi

899
Q

What is the signal transduction of Beta 1? (Gq, Gi, or Gs??)

A

Gs

900
Q

What is the signal transduction of Beta 2? (Gq, Gi, or Gs??)

A

Gs

901
Q

What is the signal transduction of Beta 3? (Gq, Gi, or Gs??)

A

Gs

902
Q

What is the signal transduction of Nicotinic Receptors?

A

Ion channels

903
Q

What is the signal transduction of M1? (Gq, Gi, or Gs??)

A

Gq (1,3,5 are all Gq)

904
Q

What is the signal transduction of M3? (Gq, Gi, or Gs??)

A

Gq (1,3,5 are all Gq)

905
Q

What is the signal transduction of M5? (Gq, Gi, or Gs??)

A

Gq (1,3,5 are all Gq)

906
Q

What is the signal transduction of M2? (Gq, Gi, or Gs??)

A

Gi (2, 4 are Gi)

907
Q

What is the signal transduction of M4? (Gq, Gi, or Gs??)

A

Gi (2 & 4 are Gi)

908
Q

What is the signal transduction of Dopamine 1 (postsynaptic)? (Gq, Gi, or Gs??)

A

Gs

909
Q

What is the signal transduction of Dopamine 2 (presynaptic)? (Gq, Gi, or Gs??)

A

Gi

910
Q

What is the signal transduction of Vasopressin 1 (vasculature)? (Gq, Gi, or Gs??)

A

Gq

911
Q

What is the signal transduction of Vasopressin 2 (renal tubules)? (Gq, Gi, or Gs??)

A

Gs

912
Q

What is the signal transduction of Histamine 1? (Gq, Gi, or Gs??)

A

Gq

913
Q

What is the signal transduction of Histamine 2? (Gq, Gi, or Gs??)

A

Gs

914
Q

Match each receptor with its physiologic action?
A2 M3 B2 B1

Increased automaticity
Coronary vasoconstriction
Skeletal muscle vasodilation
Bronchoconstriction

A

Increased automaticity - B1
Coronary vasoconstriction - A2
Skeletal muscle vasodilation - B2
Bronchoconstriction - M3

915
Q

What does parasympathetic nervous stimulation of M2 receptors cause?

A

Decreased rate, contraction, and conduction velocity

916
Q

______ nervous system of B1 receptors. atthe heart causes increased rate, contraction, and conduction velocity.

A

Sympathetic

917
Q

Do arteries and veins receive PNS input?

A

No

918
Q

Arteries and veins receive no PNS input, in general. What are the excpetions?

A

Coronary vessels (vasodilation) and cerebral vessels (receptor-specific vasodilation or vasoconstriction)

919
Q

SNS stimulation of most arterial vessels causes ______ via what receptors?

A

vasoconstriction; A1

920
Q

SNS activation of ___ receptors on veins produces venoconstriction.

A

A2

921
Q

SNS stimulation of B2 receptors on most arterial vessels produces what?

A

vasodilation

922
Q

What is the PNS effect upon airway smooth muscle and through what receptor?

A

Contraction of airway smooth muscle; M3

923
Q

SNS activity produces ____ of airway smooth muscle

A

relaxation (b2 receptors)

924
Q

SNS:
Effector - Heart
Receptor - ______

A

B1

925
Q

SNS:
Effector - Lungs
Receptor - ______

A

B2

926
Q

SNS:
Effector - GI Tract
Receptor - ______

A

A1

927
Q

SNS:
Effector - Glands
Receptor - ______

A

A1

928
Q

SNS:
Effector - Urinary Tract
Receptor - ______

A

A1, B2

929
Q

SNS:
Effector - Skin
Receptor - ______

A

A1

930
Q

SNS:
Effector - Skeletal Muscle
Receptor - ______

A

B2

931
Q

SNS:
Effector - Pupils
Receptor - ______

A

A1

932
Q

SNS:
Effector - Heart
Receptor - B1
Effect - ________

A

Positive inotropic, chronotropic, and dromotropic effect

933
Q

SNS:
Effector - Lungs
Receptor - B2
Effect - ________

A

Bronchodilation

934
Q

SNS:
Effector - GI Tract
Receptor - A1
Effect - ________

A

Vasoconstriction; Sphincter contraction

935
Q

SNS:
Effector - Glands
Receptor - A1
Effect - ________

A

Increased sweating
Decreased pancreatic activity

936
Q

SNS:
Effector - Urinary Tract
Receptor - A1, B2
Effect - ________

A

Bladder sphincter contraction
Increased renin secretion

937
Q

SNS:
Effector - Skin
Receptor - A1
Effect - ________

A

Vasoconstriction

938
Q

SNS:
Effector - Skeletal Muscle
Receptor - B2
Effect - ________

A

Vasodilation

939
Q

SNS:
Effector - Pupils
Receptor - A1
Effect - ________

A

Dilation

940
Q

PNS:
Effector - Heart
Receptor - ______

A

M2

941
Q

PNS:
Effector - Lungs
Receptor - ______

A

M3

942
Q

PNS:
Effector - GI Tract
Receptor - ______

A

M3

943
Q

PNS:
Effector - Glands
Receptor - ______

A

M1, M3

944
Q

PNS:
Effector - Urinary Tract
Receptor - ______

A

M3

945
Q

PNS:
Effector - Pupils
Receptor - ______

A

M3

946
Q

PNS:
Effector - Heart
Receptor - M2
Effect - ______

A

Negative inotropic, chronotropic, and dromotropic effect

947
Q

PNS:
Effector - Lungs
Receptor - M3
Effect - ______

A

Bronchconstriction
Increased galnd secretion

948
Q

PNS:
Effector - GI Tract
Receptor - M3
Effect - ______

A

Increased motility
Sphincter relaxation
Increased gland secretion

949
Q

PNS:
Effector - Glands
Receptor - M1, M3
Effect - ______

A

Increased salivation
Increased lacrimation
Increased pancreatic activity

950
Q

PNS:
Effector - Urinary Tract
Receptor - M3
Effect - ______

A

Bladder sphincter relaxation

951
Q

PNS:
Effector - Pupils
Receptor - M3
Effect - ______

A

Constriction