ANS Pharmacology

Question 1

Where is acetycholine found as a neurotransmitter?

Answer 1

All pre-gang autonomic fibers, all post-gang para fibers, and post-gang sympa fibers which innervate sweat glands.

Question 2

Where is norepinephrine found as a neurotransmitter?

Answer 2

post-gang sympa fibers

Question 3

Where is epinephrine found as a neurotransmitter?

Answer 3

Chromaffin cells of the adrenal medulla

Question 4

Where is dopamine found as a neurotransmitter?

Answer 4

Post-gang sympa fiber which synapse onto renal vasculature smooth muscle

Question 5

Describe the synthesis of acetycholine.

Answer 5

Choline is co-transported into neurons with Na+. In the cytoplasm choline acetyltransferase (ChAT) will trasnfer acetate from AcCoA to choline creating acetylcholine (ACh). ACh is stored in synaptic vesicles.

Question 6

Describe the release of ACh into the synapse.

Answer 6

An action potential reaches the synaptic terminal causing depolarization and opening of Ca2+ channels. Ca2+ influx leads to fusion of synaptic vesicles with the synaptic membrane. Fusion is mediated by SNARE proteins.

Question 7

Describe the effects of ACh binding to cholinergic receptors.

Answer 7

ACh diffuses across the synaptic cleft to bind either nicotinic or muscarinic AChRs. This will result in depolarization of the cellular membrane, second messenger cascade, or epinephrine release from chromaffin cells.

Question 8

What is the effect of ACh binding to pre-junctional nAChRs?

Answer 8

Mobilizes additional neurotransmitter for synaptic release.

Question 9

What is the effect of ACh binding to pre-junctional mAChRs?

Answer 9

Inhibits further release of ACh.

Question 10

Describe the termination of cholinergic signaling.

Answer 10

Acetylcholine esterase is found in the synaptic cleft. This enzyme degrades ACh into acetate and cholin. Acetate will diffuse from the synapse and choline undergoes recycling thorugh contransport with Na+.

Question 11

Describe the nicotinic AChR (nAChR).

Answer 11

These are ligand-gated ion channels that allow the passage of Na+ into the cell when activated. They are found at the NMJ, ganglia, and CNS.

Question 12

Describe the muscarinic AChR (mAChR).

Answer 12

These are seven-pass transmembrane g-protein coupled receptors which trigger second messenger cascades upon activation. M2 and M3 receptors are found at smooth muscle while M2 is found at cardiac muscle.

Question 13

Generally describe the synthesis of catecholamines.

Answer 13

All catecholamines are synthesized from tyrosine. Tyrosine –> DOPA –> Dopamine –> NE –> Epi

Note: conversion of NE to Epi only occurs in the adrenal medulla

Question 14

Describe storage of catecholamines.

Answer 14

VMAT-2 transports DA into synaptic vesicles where it is then converted into NE.

Note: VMAT-2 is promiscuous and will take anyone: DA, NE, Epi, and serotonin.

Question 15

Describe the release of catecholamines

Answer 15

This is pretty much the same as ACh

Question 16

Describe the binding of catecholamines to adrenergic receptors.

Answer 16

Catecholamines bind to GPCRs classified as alpha or beta adrenergic receptors. These receptors have second messenger actions which are inhibitory or stimulatory depending on the G alpha subunit they are associated with.

Question 17

Describe the termination of catecholamine signaling.

Answer 17

Termination of signaling occurs by reuptake, in contrast to degradative enzyme in termination of cholinergic signaling. After reuptake catecholamines are either repackaged by VMAT-2 or metabolized by monoamine oxidase (MAO), which lies on the external surface of mitochondria. Circulating catecholamines are metabolized by catechol-O-methyl transferase, which is found in cellular cytoplasms.

Question 18

What is the action of reserpine?

Answer 18

Inhibits the action of VMAT-2

Question 19

What two transporters are responsible for reuptake of catecholamines?

Answer 19

NET = NE and DAT = DA

Question 20

What is the action of cocaine?

Answer 20

Inhibition of NET

Question 21

What are the g-proteins, agonists, and responses affiliated with alpha 1 receptors?

Answer 21

G alpha q subunit which increase phospholipase C activity

Agonist = phenylephrine

Activation causes activation of muscular contraction

Question 22

What is the exception to alpha 1 receptor activation?

Answer 22

In the gut activation of alpha 1 receptors cause increased Ca+2 leading to activation of Ca2+ dependent K+ channels. Influx of K+ into these smooth muscle cells causes hyperpolarization and relaxation.

Question 23

What are the g-proteins, agonists, and responses affiliated with alpha 2 receptors?

Answer 23

G alpha i subunit which inhibits cAMP production

Agonist = clonidine

Activation causes vascular smooth muscle contraction, decreased insulin secretion, and decreased release of NE (via presynaptic alpha 2 receptors)

Question 24

What is the relative potency of NE, isoproterenol, and Epi at alpha receptors?

Answer 24

Epi =/> NE&raquo_space; Iso

Question 25

What are the g-proteins, agonists, and responses affiliated with beta 1 receptors?

Answer 25

G alpha s subunit which stimulate cAMP production

Agonist = dobutamine

Activation causes increased force of contraction in cardiac muscle, increased rate of contraction in cardiac muscle, and increased AV nodal conduction velocity.

Question 26

What are the g-proteins, agonists, and responses affiliated with beta 2 receptors?

Answer 26

G alpha s subunit which stimulates cAMP production

Agonist = terbutaline

Activation causes relaxation of bronchial, vascular, genitourinary, and gastrointestinal smooth muscle

Question 27

What are the g-proteins and responses affiliated with beta 3 receptors?

Answer 27

G alpha s subunit which stimulates cAMP production

Activation causes lipolysis

Question 28

What is the relative potency of NE, isoproterenol, and Epi at alpha receptors?

Answer 28

Beta 1 = Iso>Epi=NE
Beta 2 = Iso>Epi»NE
Beta 3 = Iso = NE > Epi

Question 29

Describe the action of D1 receptors at renal smooth muscle and its downstream effects.

Answer 29

D1 receptors in renal smooth muscle will increase cAMP when activated causing relaxation and dilation. The overall effect is natriuresis and diuresis.

Question 30

What effect would high concentrations of DA have systemically?

Answer 30

At high concentrations DA can activate alpha 1 and beta 1 receptors leading to an increase in heart rate and general vasoconstriction.

Question 31

Describe how ACh can cause systemic vasodilation.

Answer 31

Vascular smooth muscle is not parasympathetically innervated. ACh in the blood stream binds to mAChRs on endothelial cells leading to their production of NO. NO diffuses to smooth muscle cells causing relaxation.

Question 32

How does NE interact with the baroreceptor reflex?

Answer 32

Administration of NE causes increases in peripheral resistance, MAP, HR, and heart contractility. Negative feedback in response to increased MAP is mediated by baroreceptors in the aortic arch and carotid sinus. This feedback causes parasympathetic stimulation of the cardiac pacemaker resulting in decreased HR alongside increased MAP.