5-HT (Serotonin) Receptors

5-HT (Serotonin) Receptors

1. Definition, historical perspective & overview

• 5-Hydroxytryptamine (5-HT, serotonin) is an indoleamine (β-aminoethyl-5-hydroxyindole) that acts as a neurotransmitter in the CNS while also exerting prominent peripheral actions; ~95% of body 5-HT is peripheral, located in enterochromaffin (EC) cells of the GI tract and in platelet storage granules, with high CNS concentrations confined to discrete raphe nuclei (G&G 14e Ch.15, p.285).
• KDT figure: about 90% of body 5-HT is in EC cells of stomach and intestines; most of the remainder is in platelets and brain. 5-HT also occurs in wasp/scorpion sting and is widely distributed in invertebrates and plants (banana, pear, pineapple, tomato, stinging nettle, cowhage) (KDT 8e Ch.12, p.185).
• Fourteen mammalian 5-HT receptor subtypes, grouped into seven subfamilies (5-HT₁–5-HT₇), have been delineated by structural and pharmacological analysis and are encoded by separate genes — together comprising the largest known neurotransmitter/hormone receptor family (G&G 14e Ch.15, pp.285, 287).
• Historical: Vittorio Erspamer (1930s) studied EC-cell distribution and isolated enteramine (a smooth-muscle contractor); Irving Page and colleagues (Cleveland Clinic) isolated a platelet-derived vasoconstrictor in clotting blood and named it serotonin — both proved to be 5-HT in the early 1950s (G&G 14e Ch.15, p.285; KDT 8e Ch.12, p.185).
• Betty Tvorog (mid-1950s) discovered 5-HT in the brain; reserpine's behavioural effects accompanied by depletion of brain 5-HT led to the proposal of 5-HT as a CNS neurotransmitter (G&G 14e Ch.15, p.285).
• A close relative of 5-HT, melatonin, is formed by sequential N-acetylation and O-methylation and is the principal indoleamine of the pineal gland, modulating circadian rhythms (use in jet lag, insomnia) — not to be confused with the pigment melanin (G&G 14e Ch.15, p.285; KDT 8e Ch.12, p.188).