Serotonin is metabolized by monoamine oxidase, and the intermediate product, 5-
hydroxyindoleacetaldehyde, is further oxidized by aldehyde dehydrogenase to 5-
hydroxyindoleacetic acid (5-HIAA). In humans consuming a normal diet, the excretion of 5-HIAA,
is a measure of serotonin synthesis. Therefore, the 24-hour excretion of 5S-HIAA can be used as a
diagnostic test for tumors that synthesize excessive quantities of serotonin, especially carcinoid
tumor. A few foods (eg, bananas) contain large amounts of serotonin or its precursors and must be
prohibited during such diagnostic tests.
Pharmacodynamics
Mechanisms of Action
Serotonin exerts many actions and, like histamine, has many species differences, making
generalizations difficult, The actions of serotonin are mediated through a remarkably large number
of cell membrane receptors. The serotonin receptors that have been characterized thus far are
described in Table 16-3. Seven families of 5-HT-receptor subtypes (those given numeric subscripts
1 through 7) have been identified, six involving G protein-coupled receptors and one a ligand-gated
ion channel, Among these receptor subtypes, several lack any recognized physiologic function.
Discovery of these functions awaits the development of subtype-selective drugs or the mutation or
deletion of genes encoding these receptors from the mouse genome.
Table 16-3. Serotonin Receptor Subtypes.
Receptor. Postreeeptor
Subtype Mechan age ts
Raphe nuclei, 8-OH-DPAT WAY 100635
hippocampus
/Substantia nigra, 4cAMP P93129
globus pallidus,
basal ganglia
es
= =
HT — |Cortex, ucAMP.
hippocampus
system.
Platelets, smooth |G, , +IP a-Methyl-5-HT Ketanserin
muscle, cerebral
cortex, skeletal
muscle