B.2. adrenergic transmission Flashcards
agents causing presynaptic inhibitory effect
𝝰₂ M₂ H₃ Metyrosine Reserpine
agents causing presynaptic stimulatory effect
M₁ β₂ AT₁ 4' aminopyridine latrotoxin indirect-acting sympathomimetics
what is the function of NE in the synaptic cleft?
- activation of postsynaptic receptors (physiological effect)
- activation of presynaptic autoreceptors
- reptake into nerve terminal by NET, followed by MAO or COMT metabolism
- diffusion into surroundings
indirect acting sympatholytics
metyrosine
reserpine
what is metyrosine?
tyrosine hydroxylase inhibitor (rate-limiting step in endogenous catecholamine synthesis)
↓ synthesis of Dopamine, NE and EPI
what is reserpine?
VMAT inhibitor
inhibits the uptake of Dopamine into storage vesicles, resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals
what is metyrosine used for?
pheochromocytoma
what is Reserpine used for?
antihypertensive
antipsychotic
Huntington’s disease
name the adrenergic receptors and their type
"QISSS" 𝝰₁ Gq-coupled 𝝰₂ Gi- coupled β₁ Gs β₂ Gs β₃ Gs
what are the effects of 𝝰₁ receptor?
- atrial and venous vasoconstriction
- mydriasis (dilation of the pupil)
- urinary sphincter constriction
what are the effects of 𝝰₂ receptor?
- central +peripheral pre-synaptic inhibition (sympatholytic)
- ↓ insulin release
- ↓ lipolysis +FFA release
- ↓ Aqueous humour production
what are the effects of β₁ receptor?
- ↑ SA &AV rate and automaticity (positive chronotropic)
- ↑ cardiac contractility (positive ionotropic)
- ↑renin release
what are the effects of β₂ receptor?
- peripheral vasodilation
- bronchodilation
- ↑ insulin release
- ↑ lipolysis +FFA release
- ↑ Hepatic gluconeogenesis+ glycogenolysis
- ↑ Aqueous humor production
what are the effects of β₃ receptor?
lipolysis in fat cells
which enzyme converts Tyrosin to DOPA?
tyrosine hydroxylase
- rate limiting step
- inhibited by metyrosine
which enzyme converts DOPA to Dopamine in the nerve terminal?
DOPA decarboxylase enzyme
which transporter transports Dopamine into a vesicle in the nerve terminal?
VMAT (vesicular monoamine active transporter)
*reserpine inhibits
which enzyme converts dopamine into Norepinephrine inside the vesicle?
dopamine β-hydroxylase
how does NE release into the synaptic cleft happen?
by Ca² influx–> action potential–> NE is released from the vesicle to the synaptic cleft
*inhibited by bretylium
on what receptor does NE act?
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
Termination of NE
2 options:
- 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
- broken down in the synaptic cleft by COMT, then oxidized again by MAO’s.
