Introduction to Autonomic Pharmacology

Question 1

list the 4 main processes ANS regulates

Answer 1

• smooth muscle contraction / relaxation
• ALL exocrine secretions; certain endocrine secretions
• heartbeat
• certain steps in intermediary metabolism

Question 2

SNS responds to the following situations (or stresses on the body)…

Answer 2

• trauma
• fear
• hypoglycemia
• cold
• exercise

Question 3

SNS stimulation effects on:

(1) HR, BP
(2) energy metabolism
(3) blood flow/distribution
(4) pupils
(5) bronchioles

Answer 3

1- inc HR, inc BP
2- inc mobilization of energy stores, glycogenolysis and fat stores
3- divert blood from skin and internal organs –> skeletal muscle and heart
4- mydriasis (pupil dilation)
5- bronchiole dilation

Question 4

PSNS is important in (1) functions and having (2) towards the SNS.

Answer 4

(rest and digest)
1- maintain essential bodily functions: digestion, elimination of waste
2- oppose/balance SNS actions

Question 5

heart is mainly under (SNS/PSNS) control

BP is mainly under (SNS/PSNS) control

Answer 5

Heart- PSNS (M2 AChR, Gi)

BP (vasculature, α1, Gq)- SNS

Question 6

list the areas only innervated by the SNS

Answer 6

• adrenal medulla
• kidney
• pilomotor muscles
• sweat glands

Question 7

list the neuronal fibers that release ACh

Answer 7

• all preganglionic efferent ANS fibers
• all PSNS postganglionic fibers
• all somatic motor fibers to skeletal muscle

Question 8

list the neuronal fibers that release NE

Answer 8

MOST postganglionic SNS fibers (exceptions: postganglionic sweat glands ACh is released, postganglionic kidney mostly DA is released, adrenal medulla is postganglionic to release Epi./NE)

Question 9

Renal vascular smooth muscle is innervated by (SNS/PSNS/both) with postganglionic fibers releasing (2)

Answer 9

1- SNS

2- Dopamine (mostly)

Question 10

adrenal medulla is special because it is innervated by (1) and responds to (2) neurotransmitter to release (3)

Answer 10

1- preganglionic SNS fibers
2- ACh (AChN receptors)
3- Epi (80%), NE (20%)

Question 11

sweat glands are innvervated by (SNS/PSNS/both) with postganglionic fibers releasing (2) onto (3) receptors

Answer 11

1- SNS
2- ACh
3- ACh-M3

Question 12

all preganglionic ANS fibers release (1) to postganglionic neurons with (2) receptors

Answer 12

1- ACh

2- AChN(n)

Question 13

list the steps for the formation and release of ACh from neuron

Answer 13

1a) Na+/choline CHT1 symporter on axonal membrane into cytoplasm
1b) acetyl CoA from mitochondria into cytoplasm
2) choline + acetyl CoA –> ACh via ChAT enzyme
3) ACh into vesicle via VAChT antiporter; H+ out
4) Ca++ influx stimulates ACh vesicle release at synaptic membrane
5) ACh breakdown in synapse by AChE –> acetyl CoA + choline

Question 14

in the release of ACh, presynaptic membranes will have (1) receptors for ACh in order to (2)

Answer 14

1- M2 receptors (Gi)

2- inhibit ACh release (via Ca++, negative feedback)

Question 15

Describe the following:

(1) ChAT
(2) CHT1
(3) VAChT

Answer 15

1- choline acetyltransferase, forms ACh from choline + acetyl CoA
2- choline transporter, axonal choline-Na+ symporter into pre-ganglionic neuron
3- vesicular ACh transporter, ACh into vesicles in exchange for H+

Question 16

list the steps for NE formation and release form neuron

Answer 16

1) Tyr influx via System L on axonal membrane
2) Tyr -(rate-limiting)-> DOPA –> DA
3) DA into vesicle via VMAT antiporter; H+ out
4) DA –> NE w/in vesicle
5) Ca++ influx stimulates NE vesicle release into synapse
6) NE reuptake via NET, or NE diffusion away from synapse

Question 17

in the release of NE, presynaptic membranes will have (1) receptors for NE in order to (2)

Answer 17

1- α2 adrenergic receptors (Gi)

2- inhibit NE release (via Ca++, negative feedback)

Question 18

Describe the following:

(1) COMT
(2) MAO
(3) NET
(4) System L
(5) VMAT

Answer 18

1- catechol-O-methyltransferase for NE/Epi breakdown (mitochondria)
2- monoamine oxidase for NE/Epi. breakdown (ER)
3- norepinephrine transport, reuptake NE into presynaptic neuron
4- for Tyr influx
5- vesicular monoamine transporter, for DA into vesicles for NE conversion

Question 19

AChR-N receptors come in type (1) and (2). They bind to (3) ACh molecules to allow (4) to occur. [include the locations for (1)/(2)]

Answer 19

1- Nm (muscle type- at skeletal NMJ)
2- Nn (neuronal type- ANS postganglionic cells, adrenal medulla, brain)
3- 2 ACh
4- Na+ influx => depolarization
(nicotinic receptors are ION channel linked)

Question 20

AChR-M receptors are (1) type receptors with the following different types: (2), (3), (4). They are found on the following: (5).

Answer 20

1- G protein coupled receptors
2- M1 (Gq)
3- M2 (Gi)
4- M3 (Gq)
5- organs with PSNS innervation, sweat glands (SNS), some cells in CNS

Question 21

activation of cardiac M2 has the following end result

Answer 21

(Gi- note that β/γ subunits are the direct actors, not α subunit)
K+ efflux (via K+ channel) => hyperpolarization

Question 22

list the M1 locations (and functions)

Answer 22

(Gq)

• ganglia (depolarization)
• CNS (inc cognitive function)
• vomiting center (emesis)

Question 23

list the M2 locations (and functions)

Answer 23

(Gi)

• heart/atria (cardiac inhibition)
• presynaptic nerve terminals (inhibits ACh release, neg. feedback)

Question 24

list the M3 locations (and functions)

Answer 24

(Gq)

• smooth muscle (contraction)
• secretory glands (secretion)
• vascular endothelium (vasodilation, via NO on vascular smooth muscle)

Question 25

describe the function of M3 on vascular endothelial cells

Answer 25

(uninnervated M3 receptors- Gq) 1) M3 activation => inc Ca --> activates endothelial NO synthase => NO formation 2) NO diffusion to adjacent vascular smooth muscle (vessel wall) 3) NO activates guanylyl cyclase => GTP --> cGMP 4) cGMP activates cGMP-dependent protein kinase --> phosphorylation of proteins => smooth muscle relaxation = vasodilation

Question 26

describe Epi/NE binding among β-adrenergic receptors

Answer 26

(all Gs) β1/β3: equal Epi/NE affinity β2: Epi affinity >> NE [i.e. skeletal muscle vasculature responds well to circulating Epi.)

Question 27

α1/β1 adrenergic receptors are generally found in (1) α2/β2 adrenergic receptors are generall found in (2)

Answer 27

1- (Gq, Gs) adrenergic nerve terminals 2- (Gi, Gs) remote from adrenergic nerve terminals (preferential to circulating Epi)

Question 28

list the β1 locations (and functions)

Answer 28

(Gs) - heart (inc HR, force of contraction, AV conduction velocity) - juxtaglomerular cells (renin release) - adipocytes (inc lipolysis)

Question 29

list the β2 locations (and functions)

Answer 29

(Gs) - smooth muscle (relaxation) - skeletal muscle (inc glycogenolysis, inc K+ uptake) - pancreatic β-cells (inc insulin secretion, less effect than α2 dec secretion) - pancreatic α-cells (inc glucagon secretion) - liver (inc glycogenlysis, gluconeogenesis) - adipocytes (inc lipolysis)

Question 30

list the β3 locations (and functions)

Answer 30

(Gs) | adipocytes (inc lipolysis)- generally limited and unclear function

Question 31

list the α1 locations (and functions)

Answer 31

(Gq) - vascular smooth muscle (contraction) - GU smooth muscle (contraction- no urination) - liver (inc glycogenolysis, gluconeogenesis)

Question 32

list the α2 locations (and functions)

Answer 32

(Gi) - presynaptic terminals (inhibit NE release, neg. feedback) - platelets (aggregation) - adipocytes (lipolysis inhibition) - pancreatic β-cells (dec insulin secretion- larger effect than β2 inc secretion) - vascular smooth muscle (contraction)

Question 33

DA receptors important in the ANS are (1) and (2) found in (3) which functions to (4)

Answer 33

1/2- D1, D5 (inc cAMP) 3- smooth muscle of renal vasculature bed 4- relaxation

Question 34

vasculature (arterioles, veins) are predominant with ____ receptors

Answer 34

α1-adrenergic receptors (Gq)

Question 35

list the areas that predominantly have M3 receptors

Answer 35

(Gs) - ciliary muscle (lens focusing) - GI tract (peristalsis) - urinary bladder (contraction => urination) - salivary glands (inc secretion) - sweat glands (although SNS, inc secretion)