B.2. adrenergic transmission

Question 1

agents causing presynaptic inhibitory effect

Answer 1

𝝰₂
M₂
H₃
Metyrosine
Reserpine

Question 2

agents causing presynaptic stimulatory effect

Answer 2

M₁
β₂
AT₁
4' aminopyridine
latrotoxin
indirect-acting sympathomimetics

Question 3

what is the function of NE in the synaptic cleft?

Answer 3

1. activation of postsynaptic receptors (physiological effect)
2. activation of presynaptic autoreceptors
3. reptake into nerve terminal by NET, followed by MAO or COMT metabolism
4. diffusion into surroundings

Question 4

indirect acting sympatholytics

Answer 4

metyrosine

reserpine

Question 5

what is metyrosine?

Answer 5

tyrosine hydroxylase inhibitor (rate-limiting step in endogenous catecholamine synthesis)
↓ synthesis of Dopamine, NE and EPI

Question 6

what is reserpine?

Answer 6

VMAT inhibitor
inhibits the uptake of Dopamine into storage vesicles, resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals

Question 7

what is metyrosine used for?

Answer 7

pheochromocytoma

Question 8

what is Reserpine used for?

Answer 8

antihypertensive
antipsychotic
Huntington’s disease

Question 9

name the adrenergic receptors and their type

Answer 9

"QISSS"
𝝰₁ Gq-coupled
𝝰₂ Gi- coupled
β₁ Gs
β₂ Gs
β₃ Gs

Question 10

what are the effects of 𝝰₁ receptor?

Answer 10

1. atrial and venous vasoconstriction
2. mydriasis (dilation of the pupil)
3. urinary sphincter constriction

Question 11

what are the effects of 𝝰₂ receptor?

Answer 11

1. central +peripheral pre-synaptic inhibition (sympatholytic)
2. ↓ insulin release
3. ↓ lipolysis +FFA release
4. ↓ Aqueous humour production

Question 12

what are the effects of β₁ receptor?

Answer 12

1. ↑ SA &AV rate and automaticity (positive chronotropic)
2. ↑ cardiac contractility (positive ionotropic)
3. ↑renin release

Question 13

what are the effects of β₂ receptor?

Answer 13

1. peripheral vasodilation
2. bronchodilation
3. ↑ insulin release
4. ↑ lipolysis +FFA release
5. ↑ Hepatic gluconeogenesis+ glycogenolysis
6. ↑ Aqueous humor production

Question 14

what are the effects of β₃ receptor?

Answer 14

lipolysis in fat cells

Question 15

which enzyme converts Tyrosin to DOPA?

Answer 15

tyrosine hydroxylase

• rate limiting step
• inhibited by metyrosine

Question 16

which enzyme converts DOPA to Dopamine in the nerve terminal?

Answer 16

DOPA decarboxylase enzyme

Question 17

which transporter transports Dopamine into a vesicle in the nerve terminal?

Answer 17

VMAT (vesicular monoamine active transporter)

*reserpine inhibits

Question 18

which enzyme converts dopamine into Norepinephrine inside the vesicle?

Answer 18

dopamine β-hydroxylase

Question 19

how does NE release into the synaptic cleft happen?

Answer 19

by Ca² influx–> action potential–> NE is released from the vesicle to the synaptic cleft

*inhibited by bretylium

Question 20

on what receptor does NE act?

Answer 20

NE acts locally as a neurotransmitter on 𝝰 and β receptors
*in some cells in the Adrenal medulla NE is converted to Epinephrine that functions as a hormone rather than just a neurotransmitter

Question 21

Termination of NE

Answer 21

2 options:

1. most common pathway- NE is taken back into the presynaptic cleft, from there it will or Re-enter the vesicle or will be broken down by Monoamine oxidase (MAO) In the mitochondria
2. broken down in the synaptic cleft by COMT, then oxidized again by MAO’s.