Serotonergic Pathways in Brain

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Serotonergic Pathways in Brain
Location of serotonergic cell bodies and pathways
in the rat CNS. Serotonergic cell bodies are
located within the B cell groups of Dahlstrom and
Fuxe (1964), from which they project caudally to
the spinal cord and rostrally to many forebrain
structures. 5-HT-immunoreactive amacrine cells
have also been found in the retina.
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The serotonergic synapse. Illustration of the
processes of serotonin (5-HT) synthesis and
metabolism, presynaptic and vesicular 5-HT
uptake, and vesicular 5-HT release. Pre- and
postsynaptic 5-HT receptors and sites of action
of some serotonergic drugs are also shown.
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Synthesis of serotonin. Serotonin (5-HT) is
synthesized from the amino acid tryptophan in two
steps catalyzed by the enzymes tryptophan
hydroxylase and aromatic L-amino acid
decarboxylase. The cofactor for each reaction is
also shown.
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Catabolism of serotonin. Serotonin is initially
catabolized by the mitochondrial enzyme monoamine
oxidase (MAO) to yield the intermediate
5-hydroxyindoleacetaldehyde. This compound is
then rapidly converted to 5-hydroxyindoleacetic
acid (5-HIAA) by the enzyme aldehyde
dehydrogenase.
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Somatodendritic and presynaptic autoreceptors on
serotonergic neurons. Somatodendritic
autoreceptors inhibit cell firing and possess a
5-HT1A pharmacology. Presynaptic autoreceptors
inhibit 5-HT release and are either of the 5-HT1B
subtype (rats and mice) or the 5-HT1D subtype
(pigs, guinea pigs, and humans).
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Structure of the rat 5-HT1A receptor
The amino acid sequence and putative
transmembrane domains of the rat 5-HT1A receptor.
The amino acids shown in color indicate residues
in common with the hamster beta2-adrenergic
receptor. Other features include N-linked
glycoslyation sites (checkered diamonds),
putative phosphorylation sites (negative
charges), and a putative palmitoylation site
(squiggle). (After Albert, 1992.)
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Blood Platelets as a Model for Serotonergic
Neurons
Serotonergic functions in blood
platelets. Serotonin (5-HT) is transported into
platelets by a membrane transporter that is
sensitive to imipramine. Inside the platelet, the
transmitter is taken up into dense-core granules,
where it is stored with ATP, ADP, and divalent
metal cations such as Ca2 or Mg2. Following
exocytotic release, 5-HT acts on 5-HT2A receptors
to enhance platelet aggregation. 5-HT is also
degraded intracellularly by monoamine oxidase
(MAO).
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