Introduction to Autonomic Pharmacology part 2

Question 1

What happens to the NE that is taken back into the cell

Answer 1

its repackaged into vessicles by the vescular monoamine transporter

Question 2

What is MAO and COMT

Answer 2

MAO is know as monoamine oxidase

COMT is known as catechol-O-methyltransferase

Question 3

What does MAO do

Answer 3

deaminate NE, Epi, and dopamine

Question 4

Where is MAO located and what is its form

Answer 4

its located on the outer surface of the mitochondria

it has two forms: A and b

Question 5

If MAO is inhibited what happens

Answer 5

inhibitiors elevate levels of the neurotransmitters in the synapse and are useful in treating depression, Parkinson’s disease and other CNS diseas

Question 6

What is COMT and where is it located

Answer 6

an enzyme, its found in the cytoplasm of the liver cells and is involved in the metabolism of endogenous circulation and administed catecholamines by O-methylation reaction

Question 7

What is the function of COMT

Answer 7

its involved in the metabolism of endogenous circulating and administered catecholamines by O-methylation reaction

Question 8

What is the mechanism of transmitter release

Answer 8

1. the priniciple way is exocytosis– the neutrotransmitter is stored in intracellular vesicles
2. vesicles fuse transiently with cell membrane and discharge their contents, in response to increase in intracellular Ca2+ concentrations
3. monoamine transmitters leak out by carrier mediated transport as well as NO and a.a. metabolites can diffuse

Question 9

What are parasypathetic and sympathetic nerve varicosities

Answer 9

in the autonomic nervous system—long thin axons that are branched and have small enlargements or varicosities

Question 10

What is the function of varicosities

Answer 10

neurotransmitter is synthesized and stored in caricosities- 20,000 per neuron and release the transmitters into the extracellular space

Question 11

What happens to neurotransmitters after they are released from varicosities

Answer 11

they diffuse through extracellular space and affect many effector tissues cells: one neurone is capable of innervating an entire organ

Question 12

What is non-adrenergic non-cholinergic transmission

Answer 12

that autonomic transmision can not be completely blocked by drugs that abolish response to NE or Epi because there are many other mediator secreted

Question 13

How was it determined that there were more transmitters than NE and Epi

Answer 13

by fluorescence and immunocytochemical methods

Question 14

What are the most common transmitter substance; but what are the other kinds

Answer 14

peptide are the most common transmitter substance but ATP and purines are also present; neurons contains as many as five different possible transmitters

Question 15

What is the most extensively studied system containing NANC neurons

Answer 15

the enteric system in the gut wall ( in addition to cholineric and adrenergic fibers)

Question 16

What is the rule of NANC transmission

Answer 16

co-transmission is the rule rather than the exception–release of more than one neurontransmitter from the same neuron

Question 17

What is the location and function of neuropeptide Y, ATP, Dopamine, Enkephalin and related opoid peptide

Answer 17

*neuropeptide Y–

location: secretomotor neurons in the ENS

function:

1) inhibit the secretion of water and electrolyytes by the gut
2) causes long lasting vasconstriction
3) cotransmitter in many parasympathetic postganglionic neurons
4) sympathetic postganglionic noradrenergic vascular neurons

*ATP (adenosine triphosphate)—

location: cotransmitter at inhibitory ENS neuromuscular junctions

function:

1) inhibits release ACh and norepinephrine from ANS nerve endings
2) excitatory transmitter in the nerves of the vas deferens

*Dopamine

location: important postganglionic sympathetic transmitter in renal blood vessels

function:

1) a modulatory transmitter in some ganglia and the ENS

*Enkephalin and related opoid peptide

location: some secretomotor and interneuron in the ENS
function:
1) inhibit the ACh release and thereby inhibit peristalsis; may stimulate secretion

Question 18

What is the location and function of galanin, CCK, CGRP, GABA, GRP, and NO

Answer 18

–Galanin:

Location: present in secretomotor neuron

Function: may play a role in appetit-saitety mechanisms

–Cholecystokinin

Function: acts as a cotransmitter in some excitatory neuromusclar ENS neurons

—Calcitonin gene related peptide (CGRP)

Location: in the substance P in cardiovascular sensory nerve fibers, some secretomotor ENS neurons and interneurons

Function: a cardiac stimulant

—GABA ( gamma-aminobutyric acid)

Function:

1) presynaptic effects on excitatory ENS nerve terminals (not a major transmitter in the ENS)
2) relaxant effect on the gut

—gastrin releasing peptide (GRP)

Function: extremely potent excitatory transmitter to gastrin cells; known as mammalian bombesin

—NO (nitric oxide)

Function: co-transmitter at inhibitory ENS neuromuscular junction; important at sphincters

Question 19

What is the location and function of 5-HT, substance P, and VIP

Answer 19

5-HT (Serotonin)::

Function: co-transmitter at inhibitor ENS neuromuscular junctions; important at sphincters

Substance P (and related “tachykinins)::

Location: an important sensory neuron transmitter in the ENS and elsewhere

Location: CGRP in cardioivacular sensory neurons

“tachykinins”- excitaory cotransmitters with ACh at ENS neuromuscular junctions

Question 20

What is neuromodulation of synaptic transmisssion

Answer 20

its control of transmission of different levels such as autoreceptors and heteroreceptors

Question 21

What are autoreceptors and how do they work

Answer 21

neurotransmitters may act upon autoreceptors present on the presynaptic terminal to modulate its own release and uptake process

Question 22

What are heteroreceptors and how do they work

Answer 22

its a receptor regulating the synthesis and/or release of mediator other than its own ligand.

for example a2 receptors found presynaptically on cholinergic neurons activation by NE results in inhibition of ACh release

Question 23

How do the autoreceptors on cholinergic neurons work

Answer 23

heteroreceptors–the cholinergic neuron which releases ACh has an alpha-2 sympathetic receptor

Question 24

How does the receptor modulate the release of neurotransmitters

Question 25

What is another way to modulate synaptic transmission

Answer 25

by altering ion currents either hyperpolarize (elevate threshold) or depolarize (decrease threshold) of the axon terminal Of activation of second messenger systems such as cAMP or cGMP can lead to phosphorylation of various protein involved in the activity of the acon terminal such as transporters and vesicle proteins

Question 26

Explain the schema of presynaptic autoreceptors

Answer 26

regulate neurotransmitter release in adrenergic (release NE) and cholinergic neurons (ACh) A2 and B2- adrenergic receptors exist on post sympathetic nerve terminal and inhibit the release of the neurotransmitter, NE Muscarinic and nicotinic cholinergic receptors exist on postganglionic parasympathetic neuron that block release ACh. A2 adrenergic receptors also exist cholinergic neurons and inhibit Ach release--for adrenergic neurons (those that release neurotransmitters that go to adrenergic receptors)--NE cholinergic neurons (those that release neurotransmitters that go to cholinergic receptors)--ACh

Question 27

What are the two main types of Ach receptors

Answer 27

muscarinic and nicotinic receptors

Question 28

What is the alkaloid muscarine and where does it work; how is the name muscarine receptors fitting

Answer 28

the poisonous agent in toadstools-Amanita muscaria- they have little to no effect on receptors in autonomic gangia but mimics the action of ACh on the effector of smooth muscle therefore the actions of ACh on SM effector organs and on heart muscle are known as muscarinic and the receptors are know as muscarinic receptors

Question 29

What are cholinergic receptors

Answer 29

these are the ACh receptors can be divided into two main types: muscarinic and nicotinic receptors

Question 30

Why is the name nicotinic receptors fitting and how does blocking muscarinic receptors help

Answer 30

in the autonomic ganglia, the actions of ACh can be reproduced by the drug nicotine. The actions of ACh in sympathetic ganglia are referred to as nicotinic, the receptors are known as nicotinic receptors by blocking the muscarinic effects and then larger doses of ACh produce nicotinic effects. In addition with ganglionic effects, stimulation of voluntary muscle and simulation of Epi secretion from the adrenal medulla is also observed

Question 31

What are the effects of Ach on nicotinic receptors

Answer 31

nicotinic receptors are located where quicker responses are needed (adrenal gland) found in sympathetic and parasympathetic postganglionic neurons at neuromuscular junctions of skeletal muscles, and at some cholinergic synapses in the central nervous system

Question 32

What type of effects was seen with acetylcholine on the cat''s blood pressure

Answer 32

ACh causes a fall in blood pressure due to vasodilation, larger doses produce bradycardia---these are muscarinic effects

Question 33

What are the two types of cholinergic receptors

Answer 33

nicotinic and muscarinic

Question 34

What are the nicotinic receptors and what is their neutrotrasmitter

Answer 34

nicotinic ACh receptors are ligand-gated ion channels that are composed of multiple subunits (a pentamer w/' 1-4 distinict subunits--subunits around an internal channel)

Question 35

How do nicotinic receptors work, describe using the diagram

Answer 35

two ACh molecules bind to the receptor to cause the Na+ channel to open the Na+ increase with the cell, an action potential is generated leading to a response

Question 36

What are the two subtypes of nicotinic receptors

Answer 36

two subtypes of nicotinic receptors: 1) Nm found @ sketeletal muscle and neuromuscular junction 2) Nn which is neuronal subtype (ganglia and adrenal gland)

Question 37

What are muscarinic receptors and what is their neurotransmitter

Answer 37

G-protein coupled receptors that exhibit classical 7 transmembrane topology and activates second messengers

Question 38

What are the five muscarinic receptor subtypes

Answer 38

M1-M5 subtypes of muscarinic receptors

Question 39

How do M1, M3, M5 work (odd numbers)

Answer 39

the M1, M3, M5 are coupled to the stimulation of IP3/ DAG pathway via Gq

Question 40

How do M2 and M4 work (even numbers) and what is imporatant about M2 receptors

Answer 40

M2 and M4 are coupled to inhibition of cAMO production via an inhibitory G-protein M2 receptors are coupled to elevation of K+ excretion which lead of hyperpolarization via a G-protein

Question 41

What is the difference between nicotinic and muscarinic receptors; which is slower and what is this important

Answer 41

the difference is their speed of action; nicotinic receptors produces almost instantaneous responses and muscarinic receptors results in slower but more prolonged effects (why muscarinic receptors results in slower but more prolonged effects

Question 42

Summarize the location and function of nicotinic receptors

Answer 42

nicotinic receptors are located where quicker responses are needed (adrenal gland); nicotinic receptors are found in sympathetic and parasympathetic postganglion neurons, at neuromuscular junctions of skeletal muscles, and at some cholinergic synapses in the central nervous systems

Question 43

Summarize the location and function of muscarinic receptors

Answer 43

found primarily in the membranes of visceral effectors, example in the heart, gastro-intestinal track, arterioles of genitalia, iris of the eye, salivary and sweat glands, lungs airways and urinary bladder

Question 44

Or rare occasion what can Ach interact with what receptors

Answer 44

although the primary receptors at the ganglia is nicotinic can have M1 receptors; ACh interacts with Nm receptors but on rare occasions can interact with minor M1 (muscarinic) receptors

Question 45

What are the adrenergic receptors

Answer 45

receptors where epinephrine, norepinephrine, isoproteranol work on; a multitude of subfamilies and subtypes of adrenergic receptors have been identified, alquist made the first differentiation of subfamilies

Question 46

What is the order of the adrenergic agonist

Answer 46

potency of adrenergic agonists in the stimulation of smooth muscle contration in vasculature was: epinephrine\> norepinephrine\> isoproteranol (alpha receptor mediated) for the same agonist, the rank order of potency for stimulation of heart rate was: isoproteranol\> epinephrine\> norepinephrine (beta receptor mediated)

Question 47

What is the rank order of potency for stimulation of heart rate

Answer 47

isoproteranol\> epinephrine\> norepinephrine its beta receptor mediated

Question 48

How is the response of the vasculature classified compared to the heart

Answer 48

its classified as alpha-receptor mediated

Question 49

What molecular tool allowed for classification of alpha and beta receptors

Answer 49

advent of more selective compounds and the tools of molecular biology have greatly expanded these obeservation of alpha and beta receptor mediated--and even more specific sub-classification of alpha and beta receptors

Question 50

How do the adrenergic receptors work

Answer 50

all adrenergic receptors are G-protein coupled and therefor activate second messengers but they differ in which second messengar they activtate, their tissue distrbution, DNA sequence and their pharmacological profile

Question 51

How are beta adrenergic receptors classified

Answer 51

classified into three subtypes: beta1, beta2, and beta3 all three subtypes are coupled to the activation of cAMP via Gs---\> cAMP the activates protein kinase A which can phosphorylate various proteins to either activate or inhibit them

Question 52

What is the activation of beta-adrenergic receptors coupled to?.

Answer 52

activation of cAMP via Gs

Question 53

Compare the sensitivity of alpha receptors and beta receptors to which neurotransmitter

Answer 53

alpha receptors stimulated mostly by NE beta receptors more sensitive to epinephrine

Question 54

What is the rule if alpha and beta receptors are both present; give an example

Answer 54

Rule: if alpha and beta receptors are present alpha= excitation beta= inhibition For example, in skeletal muscle's arterioles, norepinephrine secreted by post-ganglionic neurons---\> vasoconstriction by alpha receptors (excitation) beta-2 receptors stimulated by circulating Epi---\> vasodilation (inhibition)

Question 55

What is an exception of the beta and alpha receptor rule

Answer 55

exceptions: beta-1 receptors stimulate heart to beat faster and stronger contraction; muscarinic-2-receptors decrease strength of contraction

Question 56

What are types of the alpha adrenergic receptors

Answer 56

alpha-1 and apha-2

Question 57

What are the subtypes for alpha-1- receptor and how do the pathways waork

Answer 57

there are 3 subtypes of alpha 1 receptors: 1A, 1B, 1D all of which are coupled to the activation of IP3 / DAG pathway---\> DAG can activate PKC and subsequent protein phosphorylation----\> IP3 can elevate intracellular Ca2+ level

Question 58

What are the subtypes for alpha-2-receptors and how do the pathways work

Answer 58

there are 3 subtypes of alpha receptors: 2A, 2B, and 2D 2A and 2B decrease intracellular Ca2+ levels 2A elevates K+ conductance (hyperpolarizing)

Question 59

Explain ocular pharmacology