Adrenergic Transmission

Question 1

varicosities

Answer 1

cell bodies in the sympathetic chain ganglion end in nerve terminals which appear varicose or beaded

norepinephrine is released here with similar mechanisms to cholinergic neuromuscular transmission

Question 2

two major differences between cholinergic and adrenergic trasmission

Answer 2

1) NE action is terminated by uptake and not by destruction as with ACh
2) presynaptic receptors for NE are of great functional importance on both adrenergic nerve endings and cholinergic nerve endings

Question 3

tyrosine and varicosities

Answer 3

tyrosine uptake from the circulation for synthesis of dopamine in the cytoplasm

Question 4

function of alpha 2 receptors in varicosities

Answer 4

act as auto-inhibitory receptors and depres neurally-evoked NE release and generally depress cellular function

Question 5

Uptake 1 or NET

Answer 5

transporter in the nerve terminal membrane with rapid, high affinity buy low capacity

requires metabolic energy and Na+

major route of NE inactivation

Question 6

substrates of Uptake 1

Answer 6

NE

epinephrine

dopamine

tyramine

ephendrine derivatives

Question 7

Uptake 2 or ENT

Answer 7

extraneuronal and low affinity, high capacity

uptake system for all catecholamines of interest

at wide neuro-effector junctions, important for terminating the action of NE

steroids are inhibitors

Question 8

If MAO and COMT are not terribly important in terminating the action of release NE, why do we have them?

Answer 8

they are important in degrading ingested amines

Question 9

inhibitors of Uptake 1

Answer 9

tricyclic antidepressants, cocaine, methylphenidate (ritalin)

Question 10

metabolism of NE

Answer 10

oxidative deamination by monoamine oxidase in the neuron and effector cell mitochondria and methylation by catechol-O-methyltransferase (COMT) in the effector cell cytoplasm

Question 11

synthesis of catecholamines

Answer 11

tyrosone -> DOPA -> Dopamine -> norepinephrine -> epinephrine

Question 13

metabolism of catecholamines

Answer 13

COMT and MAO, order is not important

COMT is a phase II methylation reaction

Question 14

VMA

Answer 14

one of the metabolites of catecholamine

acts as an index of peripheral catecholaminergic activity

one of the tests for pheochromocytoma is elevated VMA levels

for greatest sensitivity, total metabolites as well as catecholamines in the liver are measured

Question 15

MHPG

Answer 15

a metabolite of catecholamines

an index of CNS catecholaminergic activity due to an aldehyde reductase in teh CNS

Question 16

inhibition of MAO and COMT

Answer 16

drugs that act indirectly to displace NE form nerve endings such as tyramine, anmphetamines, and ependrine can have profound sympathomimetic effects when mAO is inhibited

Question 17

blockers of uptake (especially Uptake I)