Exam 3 Flashcards
(145 cards)
1
Q
what is a property of ligands and their receptors?
A
ligands can bind to multiple receptors
2
Q
what are the two types of ligand receptors?
A
metatropic and ionotropic
-meta: channel and binding site DIFFERENT proteins, GTP
-iono: channel and binding site SAME protein
3
Q
what are the 6 criteria to be a monoamine?
A
- NT are in the axon terminals
- NT is released by action potentials
- present in NT postsynaptic receptors
- must have a mechanism for termination (inactivation)
- external application mimics normal response
- receptor antagonist inhibits effects of NT and presynaptic stimulation
4
Q
what are the two different forms of monoamines (MA)?
A
catecholamines and indolamine
5
Q
whats the difference b/w a catecholamine and an indolamine?
A
catechol: 1 ring, tyrosine precursor
indole: 2 rings, tryptophan precursor
6
Q
where are monoamines found and how many are there?
A
in the CNS (midbrain, pons, medulla)
-about 1 million
7
Q
what NT are under the class catecholamines?
A
dopamine (DA)
norepinephrine (NE): nonradrenergic and adrenergic forms
epinephrine (EPI): adrenergic form
8
Q
what NT are under the class indolamines?
A
serotonin (5-HT)
melatonin (MT)
9
Q
what is the overall way monoamines are terminated?
A
presynaptic reuptake via active transport
-in the liver
10
Q
what are the two distinct ways monoamines are terminated?
A
-monoamine oxidase (MAO)
-catechol-O-methyltransferase (COMT)
11
Q
what NT does MAO terminate and where?
A
ALL: DA, NE, 5-HT
-in axon terminal and astrocytes
12
Q
what NT does COMT terminate and where?
A
catechol only: DA, NE
-in astrocytes and microglia
13
Q
what does Reserpine do to monoamines?
A
decrease NT storage by blocking the MA transporter VMAT2
-NT is degraded by MAO in axon terminal
-indirect ANT
14
Q
what does MAOI (monoamine oxidase inhibitor) do to monoamines?
A
blocks MAO from degrading NT
-indirect agonist
15
Q
what do reuptake blockers do to monoamines?
A
increase NT in the synapse
-antidepressants, cocaine, amphetamine
16
Q
what are examples of action potential independent DA and NE release?
A
amphetamine and methamphetamine
17
Q
where does dopamine come from?
A
midbrain in the CNS
18
Q
what are the three ascending pathways of dopamine?
A
Nigrostriatal Pathways
Mesolimbic Pathway
Mesocortical Pathway
19
Q
what is the nigrostriatal pathway?
A
substantia nigra -> striatum
-deals with movement (Parkinson’s)
20
Q
what is the mesolimbic pathway?
A
ventral tegmental area (VTA) -> limbic
-deals with addiction (schizophrenia)
21
Q
what is the mesocortical pathway?
A
VTA -> cortex
-deals with addiction (schizophrenia)
22
Q
how many dopaminergic types are there?
A
5 (DA-R)
23
Q
are DA-R metabotropic or ionotropic?
A
metabotropic
24
Q
what are the two main classes of DA-R and what do they do?
A
D1 family (D1 & D5): activates GS, increase cAMP
D2 family (D2, D3, D4): activates GI, decreases cAMP, opens K+ channels
25
what are examples of dopaminergic agonists and antagonists?
agonist: L-DOPA (Tx for Parkinson's)
ANT: Thorazine (D1), Haldol (D2)
26
what is the synthesis of dopamine and what are the enzymes?
tyrosine --(tyrosine hydroxylase)--> DOPA --(aromatic AA decarboxylase)--> DA
27
what is the major metabolite of DA and what does a major metabolite do?
homovanillic acid (HVA)
-you can check levels of the major metabolite in the CSF fluid to monitor levels of the NT
28
where does norepinephrine (NE) come from?
mainly the adrenal glands of the PNS (from sympathetic receptors)
-can also come from the locus coeruleus of the CNS
29
what is the receptor for NE and what are the types?
Adrenergic Receptors
-alpha-adrenoceptor
-beta-adrenoceptor
30
what do alpha-adrenoceptors do?
alpha1: Gq, increases Ca2+
alpha2: GI, decrease cAMP, opens K+ channel
31
what do beta-adrenoceptors do?
B1 and B2
-Gs, increase cAMP
32
what are examples of adrenergic agonists and antagonists?
agonists: ephedrine, mescaline
ANT: propranolol (beta blocker)
33
what receptor does epinephrine bind to and what is it made from?
same adrenergic receptors as NE
-synthesized from NE
34
what is the synthesis of NE and what are the enzymes?
tyrosine --(tyrosine hydroxylase)--> DOPA --(AADC)--> DA --(dopamine beta hydroxylase)--> NE
35
what are the NE major metabolites?
MHPG and VMA
36
where does serotonin (5-HT) come from?
the raphe nuclei in the PNS
-in the midline of the brain stem (dorsal and median)
37
what are the functions of serotonin?
breathing, eating, pain modulations, anxiety, learning, memory
38
how many receptor types are there in 5-HT?
7 types with subtypes within each type
39
are 5-HT receptors metabotropic or ionotropic? what is the exception?
metabotropic
-EXCEPT 5-HT3
40
what are the 5-HT agonists?
MDMA (Ecstasy): neurotoxicity
LSD: in 8 receptor types, 5-HT2a (hallucinations)
Phenethylamines: mescaline
Buspirone (Buspar): anxiolytic (Tx anxiety), 5-HT1a
41
what are the 5-HT inverse agonists?
Ketanserin: 5-HT2, decrease 2nd messenger systems
42
what are the 5-HT antagonists?
Risperidone: antipsychotic, 5-HT2a
43
what is the synthesis of 5-HT?
tryptophan --(tryptophan hydroxylase)--> 5-HTP --(AADC)--> 5-HT
5-HTP: hydroxytryptophan
5-HT: hydroxytryptamine
44
what is the major metabolite of 5-HT?
5-HIAA (hydroxyindoleacetic acid)
45
is acetylcholine (ACh) a type of monoamine?
NO
46
what is the ACh precursor?
choline (comes from fat in our diet)
47
what enzyme degrades ACh?
acetylcholinesterase (AChE)
-inside the presynaptic cell and on postsynaptic membrane
48
what are the two receptor types in ACh and what type of ligand receptor are they?
nicotinic (ionotropic)
muscarinic (metabotropic)
49
what is the synthesis of ACh?
choline + acetyl CoA --(choline acetyltransferase)--> ACh
50
what are the characteristics of nicotinic receptors (nACh-R)?
MULTIPLE SUBUNITS and RECEPTOR SUBUNITS
-excitatory: control Na+ and Ca2+ channels
-desensitizes: inactive and becomes active spontaneously
-depolarization block: w/ continuous stimulation, it reaches a max and impairs the action potential
51
what are the characteristics of muscarinic receptors?
5 TYPES (M1-M5)
-excitatory or inhibitory
-controls 2nd messenger systems: decreases cAMP, increases phosphoinositide activity
-G-protein coupled channel: opens K+ channel
52
what three areas is ACh distributed in the PNS and what receptor subtype are they?
-skeletal muscle: NICOTINIC
-autonomic ganglia: NICOTINIC
-parasympathetic neuroeffector: MUSCARINIC
53
what four areas is ACh distributed in the CNS and what receptor subtype are they? What are their functions?
all MUSCARINIC
-neocortex and hippocampus: memory
-striatum: movement
-lateral dorsal tegmentum: reward
-basal forebrain (BFCS): conscious arousal
54
what are ACh direct agonists?
-muscarine
-nicotine (low dose stimulates)
-succinylcholine (nACh-R, degradation resistant, muscle relaxant)
55
how is AChE inhibited?
indirectly through irreversible binding and reversible binding
56
AChE inhibition through irreversible binding
-ANTAGONIST
-binds AChE so long it can't work fast enough to replace it
-sarin and soman (nerve gases)
57
AChE inhibition through reversible binding examples
pyridostigmine: used during war to protect against gases
physostigmine: Tx for glaucoma and myasthenia gravis
neostigmine: Tx for myasthenia gravis
58
ACh direct antagonists (nicotinic and muscarinic) examples
NICO: curare (paralysis at muscle)
MUSC: atropine (antidote for nerve gas), scopolamine (antinausea)
59
ACh indirect antagonists (decreases ACh)
hemicholinium: blocks choline receptor
Botulinum Toxin: cleaves SNAREs, prevents vesicular membrane fusion
Black Widow Venom: increase of Ca2+ (influx)
60
what are unmodified AA?
includes nonessential AA (not form our diet)
-form peptides
61
what are the two excitatory AA?
work at receptors that excite, are NOT excitatory THEMSELVES!!
-glutamate (Glu)
-aspartate (Asp)
62
what are the two inhibitory AA?
GABA
glycine (Gly)
63
where is glutamate found?
only in the CNS
64
what is glutamate synthesized from?
glutamine (comes from astrocytes)
65
is glutamate released on its own?
no, its co-released with other NT (ACh, DA, 5-HT, GABA)
66
what are the three types of ionotropic glutamatergic receptors?
AMPA-R: Na+ influx
Kainate-R: Na+ influx
NMDA-R: Na+ and Ca2+ influx (hybrid receptor)
67
what are do metabotropic glutamatergic receptors do?
-decrease cAMP
-increase phosphoinositide activity
68
where is glutamate distributed? (3)
Cerebral Cortex: pyramidal neurons
Hippocampus: LTP, LTD
Cerebellum: LTD
69
why can glutamate only be distributed in these three areas?
it can't cross the BBB
70
what is excitotoxicity?
when a brain injury occurs, it increases glutamate
-leads to programmed cell death
71
what is the full name of GABA and is it an AA?
gamma-aminobutyric acid
-NOT an AA, only a NT
72
what is GABA synthesized from?
glutamate
73
what degrades GABA?
GABA-aminotransferase (GABA-T)
74
what are the two receptors for GABA?
GABA(a)
GABA(b)
75
characteristics of GABA(a)
-ionotropic
-Cl- influx which creates an IPSP
-allosteric binding
76
characteristics of GABA(b)
-metabotropic
-decreases cAMP
-opens K+ channel
77
how is GABA synthesized and what are the enzymes?
Glutamine --(glutaminase)--> Glutamate --(glutamic acid decarboxylase)--> GABA
78
what are examples of GABAergic agonists, antagonists, and inverse agonists?
agonist: benzodiazepines, barbiturates, ethyl alcohol
ANT: picrotoxin
inverse agonist: beta carboline-3-carboxylate (produces anxiety)
79
what are neuropeptides and where are they synthesized?
chains of AA
-neuromodulation
-synthesized in the soma
80
what are two common examples of neuropeptides?
-substance P
-endorphins
81
what are endorphins?
-produce analgesia (w/o pain) and euphoria :)
-co-released with NT's
-bind at opioid receptors
82
what are the opioid receptor classes? (4)
-dynorphin
-met- and leu- enkephalins
-beta endorpin
-endomorphins
83
what are the four opioid receptor subtypes?
-mu (µ), delta (δ), kapa (κ)
-nociceptin/orphanin FQ receptor (nalozone insensitive)
84
direct agonist and direct ANT of endorphins?
agonists: morphine, codeine, heroin
ANT: naloxone, naltrexone
85
what does histamine do?
-inflammatory response
-conscious arousal
86
what do purines do?
-co-released from vesicles
-movement
-make sensory and autonomic ganglia
87
what do retrograde messengers do?
send message from postsynaptic cell to presynaptic cell
-Ca2+ dependent release
-not stored in vesicle (highly lipid soluble)
-types: (NO), endocannabinoids
88
how is nitric oxide (NO) synthesized?
(NO) synthase
89
what do endocannabinoids do, how are they synthesized, and what are the two types?
-inhibit presynaptic GABA release
-synthesized through degradation of membrane
-types: anandamide, 2-AG (arachadonoylglycerol)
90
how did the autonomic NS get its name?
b/c the effectors are autonomous
-don't need a neural input to function
91
where in the body do autonomic NS control?
smooth muscle, cardio muscle, glands
92
what class of drugs impacts the autonomic NS?
psychoactive drugs
93
what type of regulation is homeostasis?
antagonistic regulation
94
what are the 3 divisions of the nervous system?
-sympathetic
-parasympathetic
-enteric
95
where does brain control of the autonomic NS come from?
hypothalamus
reticular formation (RF)
96
what is the common order of the structures in the autonomic NS?
spinal cord -> preganglionic neuron -> ganglion -> postsynaptic neuron -> effector
97
where are the ganglia in the sympathetic NS vs the parasympathetic NS?
Symp: near the spinal cord
Parasymp: near the effector
98
what are differences in the size of the dendritic trees and their neural inputs between the sympathetic and pararsympathetic NS?
symp: large dendritic trees, many neural inputs
parasymp: few dendrites, fewer neural inputs
99
does the sympathetic or parasympathetic NS have a long preganglionic neuron and a short postganglionic neuron?
parasympathetic
-sympathetic has short pregang and long postgang
100
what type of outflow does the sympathetic NS have and what does that mean?
thoracolumbar outflow
-neurons come from the thorastic and lumbar region of the spinal cord
101
where do the preganglionic neurons come from?
lateral horns of the spinal cord
102
what type of activation does the homeostatic activity have?
tonic activation (persistent activity)
-discrete (not none-or-all)
-short lasting effects
103
what type of activation does the fight/flight activity have in the sympathetic NS?
diffuse activation
-all activate strongly at the same time very quickly
-long lasting
104
what type of outflow does the parasympathetic NS have and what does that mean?
craniosacral outflow
-has cranial nerves from the brainstem
-has sacral spinal cord nerves from the lateral horns
105
what type of activation does the parasympathetic NS have?
discrete, tonic activation
-short lasting effects
106
what does the preganglionic neuron do?
release ACh
-has both types of ACh-R (nicotinic and muscarinic)
107
what does the neuroeffector synapse do?
-has axonal varicostities
-released the NT from postganglionic neuron
-the NT travels long distances
108
what does the postganglionic neuron do?
it has different NT at effectors
109
what NT is used in the parasympathetic NS?
ACh
-uses mainly muscarinic receptors (M1 & M2)
-found in GI tract and cardio system
-controls K+, Ca2+, and (NO) synthesis
110
what NT is used in the sympathetic NS?
NE
-uses both beta and alpha receptor subtypes
111
what NT is used in the Enteric NS?
ACh and NE
-uses a neuropeptide as a co-transmitter
112
what do the adrenal glands do and what is special about their neurons?
-takes ACh and turns it into NE to be released into the blood
-maintains sympathetic NS
-responsible for long lasting effects in emergencies
-only has ONE neuron
113
HEART: does in increase or decrease in sympathetic and parasympathetic NS
sym: increase
parasym: decrease
114
RESPIRATION: does in increase or decrease in sympathetic and parasympathetic NS
sym: increase
parasym: decrease
115
SALVATION: does in increase or decrease in sympathetic and parasympathetic NS
sym: increase (putrid)
parasym: decrease (profuse)
116
GI: does in increase or decrease in sympathetic and parasympathetic NS
sym: decrease
parasym: increase
117
IMMUNE SYSTEM: does in increase or decrease in sympathetic and parasympathetic NS
sym: decrease
parasym: increase
118
SWEAT GLANDS: does in increase or decrease in sympathetic and parasympathetic NS
sym: increase
parasym: NONE
119
ADRENAL GLANDS: does in increase or decrease in sympathetic and parasympathetic NS
sym: increasae
parasym: NONE
120
IRIS: does in increase or decrease in sympathetic and parasympathetic NS
sym: increase (radial)
parasym: increase (sphincter)
121
what is conscious arousal?
level of alertness and how conscious/aware you are of the things around you
-autonomic inputs
122
what are central sensory afferents? (CSA)
sensory info
-external: environment
-internal: somatosensory
123
where sensory afferents send their signal to?
-directly to the brain (rapid, point-to-point)
-to the reticular formation (slow, indirect)
124
what is the reticular activating system?
gets inputs from the sensory afferents and creates two general cortical arousal streams
125
what are the two streams in the reticular activating system?
Ventral Stream: RF --> BF
Dorsal Stream: RF --> Thalamus --> BF
126
what do the NTs (ACh, NE, 5-HT) do to arousal in the reticular formation? where in the brain does the signal come from?
ACh = increase arousal (ventral RF)
NE = increase arousal (locus coeruleus)
5-HT = decrease arousal (raphe nuclei)
127
what does ACh and GABA do in the basal forebrain?
ACh: increase arousal (inhibited by adenosine, stimulated by histamine)
GABA: modulates arousal (increase in GABA = decrease in arousal, decrease in GABA = increase in arousal)
128
what are the agonists and antagonists in the basal forebrain?
agonists: barbiturates, ETOH, benzodiazepines
ANT: picrotoxin, strychnine
129
what is pain and what is its function?
-based on individuals perception because it has many components
-subjective response
-signals for potential injury and motivates behavior
130
what is nociception?
sensation of stimulus
-detects and transduces pain into a neural signal
131
nociceptor structure and the three types
-have free nerve endings (no structures surrounding them)
-no specificity
-types: mechanical, thermal, chemical
132
what are the two branches in the anterolateral system (parallel pain pathways), and what do they detect?
Sensory Discriminative Branch: locus of stimulus, intensity, type
Affective Motivational Branch: emotion, behavior
133
where are 1st order sensory neurons located at, where to they project to, and what do they release?
-located in the unipolar dorsal root ganglia neuron
-project to gray matter of dorsal horn
-releases glutamate (fast) and substance P (slow & long)
134
where are 2nd order sensory neurons located at and where does it send its signal to?
-located at the gray part of the dorsal horn of the spinal cord
-sends signal to the anterolateral columns in two directions
135
where do the two signals in the anterolateral columns go to?
-either the brainstem periaqueductal gray (PAG)
-or thalamus -> cortex
136
what is behavioral analgesia?
decreased perceived pain w/o loss of consciousness
-stress induced
-decreases nociception and subjective experience
-TEMPORARY
137
what type of receptors does analgesia act on?
opioid-mediated receptors (Endorphins)
138
how is naloxone a direct ANT for opioids?
high affinity but low efficacy for them (wants to bind them, but produces a small effect)
-insurmountable action
139
what types of things are naloxone sensitive?
things that cause analegesia to bind to the opioid receptors
-stress-induced things
-acupuncture
-placebo effect
140
what types of things are naloxone insensitive?
hypnosis
meditation
141
what are the two analgesic mechanisms?
-opioid-mediated
-NON opioid-mediated
142
where is the opioid-mediated mechanism located at? (2 places)
-PAG of the supra-spinal cord (above SC)
-Dorsal horn of the spinal cord
143
what types of things are non opioid-mediated mechanisms?
glutamate, estrogen, cholinergic, endocannabinoids, chronic pain
144
what is the descending analgesic circuit pathway?
PAG --> activates opioid --> inhibits GABA --> active ACh --> LC --> RN --> spinal cord
145
what types of neurons increase and decrease in the spinal cord of the descending analgesic circuit?
-INCREASE of inhibitory neurons (GABA, enkephalin) through excitation (+)
-DECREASE of excitatory neurons through inhibition (-)
