Adrenergic Transmission

Question 1

Which catecholamine is formed in adrenergic postganglionic neurons?

Answer 1

norepinephrine (NE)

Question 2

which catecholamine is formed in the basal ganglia of the CNS?

Answer 2

dopamine

Question 3

which catecholamine is converted to epinephrine in the adrenal medulla?

Answer 3

norepinephrine

Question 4

What is the rate-limiting step?

Answer 4

tyrosine hydroxylase

Question 5

synthesis of epinephrine is increased by?

Answer 5

glucocorticoids

Question 6

tyrosine, dopa, and dompamine, and epinephrine (reactions 1,2,4) are where? Compared to norepinephrine (reaction 3)?

Answer 6

reactions 1,2,4 = cytosol, reaction 3 = vesicle

Question 7

Vesicular storage protects NE, Epi, and DA from what?

Answer 7

DEGRADATION by mitochondrial monoamine oxidase

Question 8

What drug inhibits storage?

Answer 8

reserpine

Question 9

What is the mechanism of reserpine?

Answer 9

irreversible inhibitor of VMAT-2; depletes catecholamines from nerve terminals and reduces SNS activity in CNS and peripheral nerves

Question 10

Characteristics of reserpine:

Answer 10

oral antihypertensive and antipsychotic; seldom used!

Question 11

What are side effects of reserpine?

Answer 11

sedation, cramping, diarrhea, psychotic depression

Question 12

T/F. NE is stored and re-used after uptake from the synapse.

Answer 12

TRUE

Question 13

NE is converted to Epi where?

Answer 13

CYTOSOL of adrenal chromatin cells

Question 14

Epi is transported back into vesicles via?

Answer 14

VMAT-2

Question 15

Negative feedback inhibition of NE release occurs from?

Answer 15

stimulation of presynaptic alpha2 receptors; activation of these receptors by NE decreases further release of NE

Question 16

Which drug stimulates NE releasE?

Answer 16

tyramine

Question 17

Which drug inhibits NE release?

Answer 17

methyldopa

Question 18

Characteristics of tyramine:

Answer 18

not absorbed in GI, amino acid found in food (protein-rich, beer, wine, cured meats, kimchee).

Question 19

Tyramine is difficult to absorb? Why is this? What is a case when it may be absorbed?

Answer 19

MAO (monoamine oxidase) limits absorption in GI; if someone is on MAO inhibitors (antidepressants) this can cause tyramine to be absorbed, which may be toxic. Those who have depression should avoid taking tyramine/eating specific foods

Question 20

Mechanism of tyramine:

Answer 20

displaces NE from vesicles and causes non-vesicular release from nerve terminals by reverse transport through the NET

Question 21

High exposures to tyramine cause cause?

Answer 21

HYPERtensive crisis from abrupt NE release

Question 22

Methyldopa inhibits release of NE. what are characteristics and who can it be used in?

Answer 22

antihypertensive; used safely during pregnancy (doesn’t hurt fetus)

Question 23

Mechanism of methyldopa:

Answer 23

prodrug converted to methyl-NE by reactions 2 and 3. methyl-NE is an alpha-2 selective adrenergic receptor agonist

Question 24

Stimulation of pre-synaptic alpha-2 receptors in the CNS do what?

Answer 24

reduce sympathetic outflow of periphery

Question 25

Side effects of methyldopa:

Answer 25

sedation, dry mouth, Parkinsonism, positive Coomb’s net in long-term use (really should not use methyldopa for long term, use for pregnancy short-term)

Question 26

Adrenergic receptor subtypes include what 2 kinds? what specific receptors are they associated with?

Answer 26

pre-synaptic (alpha 2) and post-synaptic (alpha 1, (2), beta 1, 2)

Question 27

Which adrenergic receptors are coupled to which G-proteins?

Answer 27

Alpha 1 = smooth muscle, Gq, contraction
Alpha 2 = nerves, Gi, inhibitory
Beta 1 = heart, kidney, Gs/cAMP, excitatory/contraction
Beta 2 = lung/skeletal muscle/uterus, Gs, relaxation

Question 28

Termination of adrenergic transmission:

Answer 28

neuronal re-uptake via active NE transporter, diffusion away from adrenergic receptors –> circulating NE, metabolism by liver and kidney

Question 29

Which drug inhibits the termination (re-uptake) of NE?

Answer 29

cocaine

Question 30

Mechanism of cocaine:

Answer 30

stimulant effects in CNS and periphery are due to excess NE remaining in the synapse following SNS nerve stimulation

Question 31

Simple characteristics of cocaine:

Answer 31

stimulate alpha-1 (vasoconstriction), blocks transporter = inhibits re-uptake of NE and Ep, anesthetic = numbing agent, test purity of cocaine on tongue.