Unit 2 - Autonomics IV Flashcards
explain synthesis of NE and E in adrenergic varicosity?
tyrosine (into cytoplasm) –> DOPA –> dopamine –> NE (vesicle) –> E (adrenal medulla)
is NE or E a neurotransmitter or a neurohormone?
NE is a neurotransmitter
E is a neurohormone
what is the receptor interaction and effector cell response of NE and E?
second messenger amplification
how do D1 (dopamine) exert its second messenger effect?
stimulatory GPCR increases cAMP (like beta1/2/3)
what is the adrenergic receptor excitation response?
constriction; Ca++ is made available to myofibrils and increases tension
-Ca++ from intracellular stores and/or transport from extracellular
what is the adrenergic receptor inhibition response?
relaxation; Ca++ is made unavailable to myofibrils and reduces tension
-Ca++ is taken into intracellular stores and/or pumped out
what is the adrenergic receptor metabolic response?
activation of AC
- increased liver glycogenolysis
- increase in plasma glucose and FFA
what are the 3 ways specifically NE can “terminate” its action?
- neuronal reuptake (neuron-specific)
- effector cell uptake (non-specific and high capacity); extra-neuronal
- diffusion into capillaries
what is the primary mechanism for terminating ACh? how is this different from NE?
enzymatic hydrolysis
-NE is reuptake
what and where is MAO?
monoamine oxidase on mitochondria surface
-metabolize NE, E, and other exogenous adrenergic drugs
what and where is COMT?
catechol-o-methyltransferase in cytoplasm of many cells, especially liver
-metabolize NE, E, and other exogenous adrenergic drugs
what are the major metabolites of NE/E that are measured in urine/plasma?
normetanephrine, metanephrine, VMA, MHPG
-for diagnostic purposes (increased plasma metanephrine indicates pheochromocytoma)
what does alpha-me-tyrosine do to modify chemical transmission?
decreases synthesis of NE (sympathetic) by decreasing pre-synaptic Ca++ influx
what does amphetamine do to modify chemical transmission?
increases release of NE (sympathetic)
what does isoproterenol do to modify chemical transmission?
combine with receptor to increase NE (sympathetic)
-increases post-synaptic Ca++ influx and second messengers
what does propranolol do to modify chemical transmission?
antagonist to beta-receptor sites to decrease NE (sympathetic)
-decreases post-synaptic Ca++ influx and second messengers
what does cocaine do to modify chemical transmission?
increases termination step such that synapse activity increases
what is the prominent effector organ and response to receptor activation of beta 1?
heart - increased heart rate and force of contraction
kidney - renin secretion
what is the prominent effector organ and response to receptor activation of beta 2?
arterioles (and arteries in skeletal muscle, coronary) - dilation
bronchial muscle - relaxation
pregnant uterus - N/A
several other sites - metabolic effects increase
what is the prominent effector organ and response to receptor activation of beta 3?
adipose tissue (lipocytes) - lipolysis and thermogenesis increase
what is the prominent effector organ and response to receptor activation of alpha 1?
arterioles in skin, mucosa, viscera, and kidney - constriction (resistance vessels)
veins - constriction
uterus and spleen - contraction
what is the prominent effector organ and response to receptor activation of alpha 2?
presynaptic nerve endings - inhibit NE release and ACh release (gut)
postsynaptic in CNS - decreased peripheral sympathetic tone
what is the prominent effector organ and response to receptor activation of D1?
renal, mesenteric, and cerebral arterioles - dilation
what are the agonist/antagonist for a1?
agonist: phenylephrine
antagonist: prazosin
what are the agonist/antagonist for a2?
agonist: clonidine
antagonist: yohimbine
what are the agonist/antagonist for D1?
agonist: fenoldopam
antagonist: N/A
what are the agonist/antagonist for B1?
agonist: dobutamine
antagonist: atenolol
what are the agonist/antagonist for B2?
agonist: albuterol
antagonist: butoxamine
what are the agonist/antagonist for B3?
N/A for both
what are the agonist/antagonist for BOTH B1/2?
non-selective
agonist: isoproterenol
antagonist: propranolol
explain presynaptic and postsynaptic autoreceptor regulation of NE release?
stimulation of presynaptic a2 receptors inhibits NE release from nerve terminal, while drugs that block postsynaptic a2 receptors enhance NE release
how are organ responses to neurotransmitters/drugs determined?
by differences in receptor populations and receptor densities
explain the adrenergic receptors on skeletal muscle vessels?
have both a1 and B2
- low concentration: B2 (lower threshold, for physiologic response from sympathetic (adrenal) stimulation) –> relaxation and dilation
- high concentration: a1 (higher threshold and “dominant constriction” only seen in high pharmacological EPI in lab or shock
what is the guiding principle to therapeutic drugs?
selectivity to get max effects with minimum side effects
for NE drugs, what does methylation at N seem to do?
NE (no methyl) is a1/2 (and less so B1)
E (1 methyl) is a1/2 and B2
isoproterenol (3 methyl) is B1/2 only (no a1 b/c too much methyl)
what are the characteristic sympathomimetics for phenylephrine?
a1
what are the characteristic sympathomimetics for clinidine
a2
what are the characteristic sympathomimetics for NE?
a1, B1, (a2)
what are the characteristic sympathomimetics for E?
a1, B1, B2, (+a2)
what are the characteristic sympathomimetics for isoproterenol?
B1/2
what are the characteristic sympathomimetics for dopamine
D1, a1, B1
what are agonist potencies at adrenergic receptors for B1?
ISO > E >= NE > D
what are agonist potencies at adrenergic receptors for B2?
ISO > E»_space; NE»_space; D
what are agonist potencies at adrenergic receptors for a1?
E >= NE > D»_space; ISO
what are agonist potencies at adrenergic receptors for a2?
CLON > E >= NE»_space; ISO
