Pharmacology of the Autonomic Nervous System (ANS)

Question 1

ANS subdivisions

Answer 1

• Sympathetic (thoracolumbar, fight or flight)
• Parasympathetic (craniosacral, rest and digest)

Question 2

β1 on heart sinoatrial node

Answer 2

Increase in heart rate

Question 3

M2 in heart sinoatrial node

Answer 3

Decrease in heart rate

Question 4

β1 in heart atria

Answer 4

Increase in contractility and conduction velocity

Question 5

M2 in heart atria

Answer 5

Decrease in contractility

Question 6

β2 in lungs (tracheal and bronchial)

Answer 6

Relaxation

Question 7

M2=M3 in lungs (bronchial and trachial)

Answer 7

Contraction

Question 8

α1 in Eye (radial muscle “iris”)

Answer 8

Contraction (mydriasis)

Question 9

M3, M2 in sphincter muscle (iris)

Answer 9

Contraction (miosis)

Question 10

β2 in ciliary muscle of eye

Question 11

M3, M2 for ciliary muscle of eyes

Answer 11

Contraction for near vision

Question 12

Parasympathetic

Answer 12

Neurotransmitters: ACh
Receptors: nAChR, mAChR

Question 13

Sympathetic

Answer 13

Neurotransmitters: NE > Epi (DA); ACh
Receptors: α, β, (D), nAChR, mAChR

Question 14

Acetylcholine (cholinergic)

Answer 14

• The major neurotransmitter of the parasympathetic nervous system
• All preganglionic autonomic fibers
• All postganglionic parasympathetic fibers
• Few postganglionic sympathetic fibers (sweat glands)

Question 15

Norepinephrine (adrenergic)

Answer 15

• The major neurotransmitter of the sympathetic nervous system
• The vast majority of postganglionic sympathetic fibers

Question 16

Epinephrine (adrenergic)

Answer 16

•Synthesis only occurs in the adrenal medulla and in a few epinephrine-containing neuronal pathways in the brainstem

Question 17

Dopamine (dopaminergic)

Answer 17

• NE and Epi precursor
• Acts on the CNS and renal vascular smooth muscle

Question 18

Co-neurotransmitters

Answer 18

ATP, neuropeptide Y, vasoactive intestinal peptide, substance P, others

Question 19

Junctional transmission

Answer 19

1) Synthesis of acetylcholine (ACh)
2) Storage
3) Release
4) Destruction

Question 20

nAChR (ionotropic)

Answer 20

Ion channels (fast) -Acetylcholine (Nicotine)

CNS
Autonomic ganglia (NN)
-Excitatory

Adrenal medula (NN)

-Release of
catecholamines

Question 21

mAChR (metabotropic)

Answer 21

G Protein coupled receptor - Acetylcholine (Muscarine)

CNS
Autonomic ganglia
Effector organs (cardiac and
smooth muscle, gland cells,
nerve terminals)

Sweat glands

Sweat secretion

Question 22

M2 on Heart, nerves, smooth muscle

Answer 22

GPCR, Gi/o

Inhibition of adenylyl cyclase (AC); ↓cAMP production, activation of K+
channels

Question 23

M3 on Glands, smooth muscle, endothelium

Answer 23

GPCR, **Gq/11 **

Activation of PLC; IP3, DAG cascade

Question 24

Junctional transmission

Answer 24

Question 25

Adrenergic nerve terminal

Answer 25

1) Synthesis 2) Storage 3) Release 4) Reuptake

Question 26

Termination of catecholamine signaling

Answer 26

Reuptake into nerve terminals * Major mechanism that terminates the actions of catecholamines * NET (norepinephrine transporter) and DAT (dopamine transporter) * After reuptake, catecholamines are stored in vesicles by the VMAT-2 **Metabolism of catecholamines (2 main enzymes)** •Monoamine oxidase (MAO) •Catechol-O-methyltransferase (COMT) ``` \*In contrast to cholinergic signaling, termination of catecholamine action by degradative enzymes (i.e., AChE) is nonexistent in adrenergic signaling ```

Question 27

α-receptors

Answer 27

* GPCR * Pre- and postjunctional * Two major subtypes (α1,α2)

Question 28

β-receptors

Answer 28

* GPCR * Pre- and postjunctional * Three major subtypes (β1, β2, β3)

Question 29

Adrenergic signaling

Answer 29

**Na+-dependent tyrosine transporter** •Transports tyrosine into the nerve terminal **Vesicular monoamine transporter (VMAT-2)** •Transports NE, Epi, DA, and serotonin into vesicles (promiscuous) Release upon action potential and Ca2+ influx **NE transporter (NET)** _*\*Cocaine inhibits this giving sympathetic effects*_ •Imports NE into the nerve terminal •DAT imports DA into the nerve terminal

Question 30

**Alpha1** adrenergic receptor

Answer 30

**Gq** ↑phospholipase C, IP3 and DAG, **intracellular Ca2+** **Epi** ≥ NE \>\> Isoproterenol Phenylephrine smooth muscle - contraction Intestinal smooth muscle - hyperpolarization and relaxation **Heart - Increased contractile force; arrhythmias**

Question 31

Alpha2 adrenergic receptor

Answer 31

**Gi, Go** ↓adenylyl cyclase ↓cAMP Epi ≥ NE \>\> Iso Clonidine **Vascular smooth muscle** Contraction

Question 32

Beta1 adrenergic receptor

Answer 32

Gs ↑adenylyl cyclase, cAMP, Ltype Ca2+ channel opening Iso \> Epi = NE Dobutamine **Juxtaglomerular cells** Increased renin secretion **Heart** Increased force and rate of contraction and AV nodal conduction velocity

Question 33

Beta2 adrenergic receptor

Answer 33

**Gs** ↑adenylyl cyclase, cAMP, Ltype Ca2+ channel opening Iso \> Epi \>\> NE Terbutamine **Smooth muscle (vascular, bronchial, GI, GU)** Relaxation

Question 34

Beta3 adrenergic receptor

Answer 34

**Gs** ↑adenylyl cyclase, cAMP, Ltype Ca2+ channel opening Iso = NE \> Epi **Adipose tissue** Lipolysis

Question 35

Sympathomimetic agents: drugs that mimic or enhance α-and β-receptor stimulation

Answer 35

**Epinephrine** (α1 = α2, β1 = β2) **Norepinephrine** (α1 = α2, β1 \>\> β2) **Isoproterenol** (β1 = β2 \>\>\>\> α)

Question 36

Primary Tissue Locations of Adrenergic Receptor Subtypes

Answer 36

Question 37

Rules of thumb for smooth muscle and autonomic receptors

Answer 37

**Alpha-1 (α1) receptors** •Stimulate contraction of all smooth muscle •Vascular smooth muscle – vasoconstriction **Beta-2 (β2) receptors** •Relax smooth muscle – vasodilation **Muscarinic receptors** •Contract smooth muscle (different intracellular signal than α1 receptors) _(Depends on relative receptor density.)_

Question 38

Response of blood vessels to autonomic nerve impulses

Answer 38

•Blood vessels are innervated by adrenergic receptors, which cause vessel constriction when activated (sympathetic) * Smooth muscle of blood vessels is NOT innervated by parasympathetic neurons * Neither mAChRs nor nAChRs are found on smooth muscle of blood vessels •Blood vessels relax in response to parasympathetic release of ACh as long as the epithelium is intact •**Apparent discrepancy** – ACh & muscarinic agonists given IV cause vasodilation due to release of nitric oxide (NO)

Question 39

mAChRs, EDRF (NO), and vessel relaxation

Answer 39

Activation of mAChRs on epithelial cells causes production and release of **endothelium-derived relaxing factor** (EDRF), also known as **nitric oxide** (NO) Stimulation of NO release can occur from ACh, vasoactive products, and physical stimuli. Nitroglycerin is similar to the NO as it helps open up the smooth muscle vessels.

Question 40

Adrenal medulla

Answer 40

**•Sympathetic innervation** * Epi and NE release is triggered _by the release of ACh from the preganglionic fibers_ * ACh binds to NNAChRs (*on chromaffin cells*) and produce a localized depolarization •Release is approximately: **80% Epi** 20% NE

Question 41

Baroreceptor reflex as an example of compensatory changes in the ANS

Answer 41

Balance between sympathetic and parasympathetic. When we're laying down and everything is vasodilated. Blood pressure is low when relaxing. When we get up the blood pressure goes up.