Lecture 7 Part 3 Flashcards
explain how norepinephrine is synthesized
tyrosine and sodium are transported into the nerve terminal by an A transporter
tyrosine hydroxylase catalyzes the conversion of tyrosine to Dopa, which then becomes DOPAMINE through Dopa decarboxylase
Dopamine enters a vesicle through VMAT in exchange for a hydrogen ion. there, it gets converted to NOREPINEPHRIN by Dopamine B-hydroxylase
what can inhibit tyrosine hydroxylase?
metyrosine
tyrosine won’t be converted to Dopa and NE can’t be synthesized
what can inhibit the transport of dopamine into a vesicle through VMAT transporter?
Reserpine
explain the release of norepinephrine
released also through the influx of calcium and VAMPS/SNAPS
binds to ADRENOCEPTORS
after NE has been synthesized and released, explain its potential fates
-usually recycled back into the nerve terminal through NET (norepinephrine transporter)
-can be released by diffusion and broken down (after binding adrenoceptors)
-can bind back to NE autoreceptor
what inhibits the release of NE in vesicles by blocking VAMPS and SNAPS
bretylium and guanethidine
what blocks the reuptake of norepinephrine through NET?
what is the result of this?
cocaine
tricyclic antidepressants
this causes NE to stay in the synaptic cleft for longer and binds to the postsynaptic neuron for a longer period of time
in which cases is norepinephrine the final product?
in which cases is epinephrine the final product?
in which cases is DOPAMINE the final product?
NE in MOST sympathetic postganglionic neurons
in the adrenal medulla and certain areas of the brain - epinephrine
in dopaminergic neurons - ends with dopamine synthesis
how is NE converted to epinephrine and where does this occur?
through Phenylethanolamine-N-methyltransferase
occurs mainly in adrenal medulla and some areas of the brain
true or false
phenylethanolamine-N-methyltransferase is a phase 2 enzyme
true
normally, what is the ration of norepinephrine to epinephrine
80% NE
20%E
besides going through dopamine, explain another pathway of NE synthesis, starting from tyrosine
tyrosine is converted to tyramine by L-amino acid decarboxylase
Tyramine is converted to Octopamine by Dopamine B-hydroxylase
Octopamine is converted to NE through Hydroxylase from the liver
can NE ever be released through a calcium INDEPENDENT process?
yes
indirectly acting and mixed sympathomimetics such as tyramine, amphetamines, and ephedrine
excellent substrate for monoamine transporter and are taken inside the nerve terminal and remove NE from vesicles and release it
____________ inhibits monoamine oxidase and enhances NE and dopamine neurotransmission
Amphetamine
what does amphetamine do in relation to NE?
inhibits monoamine oxidase and enhances NE and dopamine neurotransmission
how many ways can noradrenergic transmission be terminated ? name them
2:
reuptake into the nerve terminal by NET or into other cells
simple diffusion away from the receptor site (eventually metabolized in the plasma or liver)
what is the RATE LIMITING STEP in catecholamine synthesis?
the conversion of tyrosine to dopa by tyrosine hydroxylase
the rate limiting step of catecholamine synthesis can be inhibited by…..
metyrosine
what is VMAT?
what can inhibit it?
VMAT = vesicular monoamine transporter
-importer for catecholamines into the vesicle
can be inhibited by RESERPINE ALKALOIDS
True or false
NET is partially responsivle for the termination of synaptic activity of norepinephrine
true
the _______ and the endocrine system are integrated
ANS
what is the function of aldosterone
to maintain fluid in the body
what are autoreceptors?
presynaptic receptors that respond to the primary transmitter substance released by the nerve ending
part of negative feedback loop
what are heteroreceptors?
regulatory receptors on nerve terminals that respond to many substances other than the primary neurotransmitter
how do local anesthetics, tetrodotoxin, and saxitoxin affect neurotransmitter synthesis?
name its site
they affect the propagation of an action potential by blocking voltage gated sodium channels and blocking conduction
located in nerve axons
explain what type of drugs inhibit transmitter synthesis and how
metyrosine - inhibits tyrosine hydroxylase and blocks catecholamine synthesis
hemicholiniums – blocks the uptake of choline, resulting in slow synthesis
what is the site of hemicholiniums?
cholinergic nerve terminals
membrane
what is the site of metyrosine?
adrenergic nerve terminals
adrenal medulla
cytoplasm
what drugs affect transmitter storage and how?
vesamicol - prevents the storage and depletes
reserpine - prevents the storage and depletes
explain the site of vesamicol and reserpine
vesamicol – cholinergic terminals, VAT on vesicles
reserpine - adrenergic terminals, VMAT on vesicles
what drugs affect transmitter RELEASE? what is their site?
MANY DRUGS - nerve terminal membrane receptors. modulate the release of the transmitter
w-conotoxin GVIA4 in particular works at nerve terminal calcium channels and thus reduces transmitter release
botulinum toxin prevents the release of acetylcholine from cholinergic vesicles
what is a-latrotoxin?
what is its site and what does it do?
located at cholinergic and adrenergic vesicles
affects transmitter release by causing explosive transmitter release
name 2 drugs that PROMOTE neurotransmitter release
where are they located?
located at adrenergic nerve terminals
tyramine and amphetamine
name drugs that inhibit the reuptake of NE through NET at adrenergic nerve terminals
what is the effect?
cocaine
tricyclic antidepressants
SNRI antidepressants
results in INCREASED NE EFFECT on the postsynaptic receptors
what is the effect of NE on alpha receptors?
causes contraction
what is the effect of phentolamine on alpha receptors?
PREVENTS the activation of alpha receptors
name 2 drugs that act on alpha receptors and their function
norepinephrine binds alpha receptors and causes contraction
phentolamine binds alpha receptors and prevents their activation
name 2 drugs that bind adrenergic Beta receptors and their effect
isoproteronol - activates adenylyl cyclase
propanolol - binds beta receptors and PREVENTS their activation
explain the action of nicotine
binds nicotinic receptors and opens ion channels in the postsynaptic membrane
what is the location of nicotinic receptors
nicotinic cholinergic junctions in autonomic ganglia and neuromuscular end plates
explain the action of Tubocurarine
prevents the activation of nicotinic receptors at neuromuscular end plates
name 2 drugs that bind muscarinic receptors and explain what they do
bethanechol - activates muscarinic receptors
atropine - binds muscarinic receptors and PREVENTS their activation
name the sites of bethanechol and atropine
muscarinic parasympathetic effector cells, such as smooth muscle and glands
