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7c biochemical events at diff synapses (cholinergic synapse (the release…
7c
biochemical events at
diff synapses
glutamatergic synapse
glutamate (glu)
released into the synaptic cleft
by Ca2+ dependent exocytosis
released Glu can act on
ionotropic & G-protein coupled receptors
on the postsynaptic neuron
synaptic transmission is terminated by
the active transport of Glu
via Na+ dependent glutamate transporters
located on membranes of
the presynaptic terminal
Glu(n) & glia Gl(g)
in glia,
Glu is converted to glutamine (Gln)
by the enzyme
glutamine synthetase
Glu then diffuses into the nerve terminal
-where its hydrolyzed back into Glu
by the enzyme
glutaminase
in the nerve terminal
Glu is highly concentrated in to
synaptic vesicles
by a vascular glutamate transporter
(pakaged)
cholinergic synapse
choline is transported into the
presynaptic terminal
by a Na+ dependent
choline transporter(CHT)
which can be blocked
by the drug
hemicholinium
Acetylcholine (A-ch) is
synthesized frm
choline & acetyl Co-A (AcCoA)
by the enzyme
choline acetyltransferase(ChAT)
in the cytoplasm
A-ch is then transported
frm the cytoplasm
into vesicles
by the vesicle-associated transporter(VAT)
with
peptides(P)
&
adenosine triphosphate(ATP)
this step can be blocked by the drug
vesamicol
A-ch is released frm the nerve terminal
when voltage sensitive
Ca2+ channels open
which allows the influx of Ca2+
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the release Ach can act on either
muscarinic G protein coupled receptors
on the postsynaptic target
(eg.smooth muscle)
nicotinic ionotropic receptors
in autonomic ganglia
end plate of skeletal muscle
in the synaptic junction,
A-ch is readily metabolised
into acetate & choline
by the enzyme
acetycholinesterase
autoreceptors
&
heteroreceptors
on the presynaptic nerve ending
modulate neurotransmitter release
noradrenergic synapse
Tyrosine (Tyr)
is transported into the
noradrenergic nerve terminal
by a Na+ dependent carrier (A)
metyrosine
blocks the action of
tyrosine hydroxylase (TH)
which is the rate limiting step
in the production of
catecholamines
(Tyrosine into dopa & then dopamine)
dopamine is
transported frm the cytoplasm
into the vesicle by the
vascular monoamine transporter (VMAT)
NE & other amines can also be
carried by VMAT
which may be blocked by the drug
reserpine
Dopamine is converted to NE in the vesicle
An AP opens voltage sensitive Ca2+ channels
to allow an influx of Ca2+
the vesicles then fuse with the surface membrane
to trigger expulsion of
NE with
peptides (P)
& ATP
this process involves
synaptosome -associated proteins (SNAPs)
&
vesicle-associated membrane proteins(VAMPs)
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NE can also diffuse out of the cleft
or
be transported back into the
nerve terminal by the
norepinephrine transporter (NET)
NET can be blocked by
cocaine &
tricyclic antidepressants
Autoreceptors & heteroreceptors
on the presynaptic nerve ending
modulate neurotransmitter release.
serotonic synapse
5-HT released
into the nerve terminal
can act on G-protein-coupled receptors
on the postsynaptic neuron
5-HT can also diffuse out of the cleft
or be transported back into the
nerve terminal by the 5-HT transporter
5-HT can act on
presynaptic autoreceptors to
inhibit further
neurotransmitter release
cytoplasmic 5-HT
is either
sequestered in vesicles
as described
or
metabolized to
5-hyroxyindole acetaldehyde
by
mitochondrial monoamine oxidase (MAO)