Adrenergic Transmission Flashcards
Which catecholamine is formed in adrenergic postganglionic neurons?
norepinephrine (NE)
which catecholamine is formed in the basal ganglia of the CNS?
dopamine
which catecholamine is converted to epinephrine in the adrenal medulla?
norepinephrine
What is the rate-limiting step?
tyrosine hydroxylase
synthesis of epinephrine is increased by?
glucocorticoids
tyrosine, dopa, and dompamine, and epinephrine (reactions 1,2,4) are where? Compared to norepinephrine (reaction 3)?
reactions 1,2,4 = cytosol, reaction 3 = vesicle
Vesicular storage protects NE, Epi, and DA from what?
DEGRADATION by mitochondrial monoamine oxidase
What drug inhibits storage?
reserpine
What is the mechanism of reserpine?
irreversible inhibitor of VMAT-2; depletes catecholamines from nerve terminals and reduces SNS activity in CNS and peripheral nerves
Characteristics of reserpine:
oral antihypertensive and antipsychotic; seldom used!
What are side effects of reserpine?
sedation, cramping, diarrhea, psychotic depression
T/F. NE is stored and re-used after uptake from the synapse.
TRUE
NE is converted to Epi where?
CYTOSOL of adrenal chromatin cells
Epi is transported back into vesicles via?
VMAT-2
Negative feedback inhibition of NE release occurs from?
stimulation of presynaptic alpha2 receptors; activation of these receptors by NE decreases further release of NE
Which drug stimulates NE releasE?
tyramine
Which drug inhibits NE release?
methyldopa
Characteristics of tyramine:
not absorbed in GI, amino acid found in food (protein-rich, beer, wine, cured meats, kimchee).
Tyramine is difficult to absorb? Why is this? What is a case when it may be absorbed?
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
Mechanism of tyramine:
displaces NE from vesicles and causes non-vesicular release from nerve terminals by reverse transport through the NET
High exposures to tyramine cause cause?
HYPERtensive crisis from abrupt NE release
Methyldopa inhibits release of NE. what are characteristics and who can it be used in?
antihypertensive; used safely during pregnancy (doesn’t hurt fetus)
Mechanism of methyldopa:
prodrug converted to methyl-NE by reactions 2 and 3. methyl-NE is an alpha-2 selective adrenergic receptor agonist
Stimulation of pre-synaptic alpha-2 receptors in the CNS do what?
reduce sympathetic outflow of periphery
Side effects of methyldopa:
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)
Adrenergic receptor subtypes include what 2 kinds? what specific receptors are they associated with?
pre-synaptic (alpha 2) and post-synaptic (alpha 1, (2), beta 1, 2)
Which adrenergic receptors are coupled to which G-proteins?
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
Termination of adrenergic transmission:
neuronal re-uptake via active NE transporter, diffusion away from adrenergic receptors –> circulating NE, metabolism by liver and kidney
Which drug inhibits the termination (re-uptake) of NE?
cocaine
Mechanism of cocaine:
stimulant effects in CNS and periphery are due to excess NE remaining in the synapse following SNS nerve stimulation
Simple characteristics of cocaine:
stimulate alpha-1 (vasoconstriction), blocks transporter = inhibits re-uptake of NE and Ep, anesthetic = numbing agent, test purity of cocaine on tongue.
