| The amino acid tryptophan is converted to 5-hydroxytryptophan by the
enzyme tryptophan hydroxylase (1) in the rate limiting step in 5-HT synthesis.
5-hydroxytryptophan is then converted to 5-HT by aromatic amino acid decarboxylase
(2). 5-HT is then actively transported into vesicles (3). The opening
of a voltage sensitive calcium channel (4) in response to depolarisation
causes the release of 5-HT from the storage vesicles into the synaptic
cleft. 5-HT then causes the depolarisation or hyperpolarisation
of target neurones via post synaptic receptors (5) as well as acting on
presynaptic receptors (6) which autoregulate 5-HT release via G protein
coupling to adenylate cyclase or phospholipase C, depending on their sub-type.
5-HT then undergoes reuptake via transporters on the presynaptic membrane
(7) which use a sodium ion gradient to fuel the movement of 5-HT.
These transporters can also leak cytoplasmic stores of 5-HT into the synaptic
cleft (8)t. Once back inside the presynaptic neurone 5-HT is either
repackaged into storage vesicles for re-release or it is metabolised by
monoamine oxidase (9) to 5-hydroxyindolacetic acid (5-HIAA), which is the
major metabolite of 5-HT. |
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