Pathophysiological role of the serotonin system in malignant hyperthermia

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Abstract
Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic amine that is distributed widely in various body tissues and cell types1 and possesses a diversity of pharmacological effects at both central and peripheral sites. 5-HT is involved in the control of temperature regulation, cardiovascular function, muscle contraction and endocrine regulation. Peripherally, 5-HT appears to play a major role in platelet homeostasis and the motility of the gastrointestinal tract. Furthermore, 5- HT exerts important effects on skeletal muscles. Synthesis and metabolism 5-HT is synthesized in situ from the amino acid precursor tryptophan. The conversion of tryptophan to 5-hydroxy- tryptophan is mediated by a tryptophan hydroxylase. 5- Hydroxytryptophan is subsequently decarboxylated to 5- hydroxytryptamine. 5-HT is then metabolized by oxidative deamination by the A enzyme of monoamine oxidase in the liver; the 5-hydroxyindoleacetaldehyde formed from this process is then oxidized to 5-hydroxyindole-3-acetic acid. 5-HT is stored in intracellular vesicles until depolarization of the neurone causes the release of this neurotransmitter into the synapse. Once 5-HT is released into the synapse, its function is terminated rapidly by its presynaptic reuptake into the neurone.