5-HT receptor subtypes
The actions of 5-HT are mediated by a range of different 5-HT receptors. The 5-HT receptors are classified into seven main receptor subtypes, 5-HT1–7. Six of the seven subtypes are G-protein-coupled receptors; 5-HT3 is a ligand-gated cation channel. 5-HT1 receptors occur primarily in the brain and cerebral blood vessels (5-HT1D only), where they mediate neural inhibition and vasoconstriction. They function mainly as inhibitory presynaptic receptors, linked to inhibition of adenylate cyclase. Specific agonists at 5-HT1 receptors include sumatriptan (used in migraine therapy) and buspirone (used in the treatment of anxiety). Spiperone and methiothepin are specific antagonists of 5-HT1 receptors. 5-HT2 receptors are found in the CNS and in many peripheral sites. They act through phospholisae C to produce excitatory neuronal and smooth muscle effects. Specific ligands at 5-HT sites include LSD – acting as an agonist in the CNS and as an antagonist in the periphery – and ketanserin and methysergide (both antagonists). 5-HT3 receptors occur mainly in the peripheral nervous system, particularly on nociceptive afferent neurones and on autonomic and enteric neurones. The effects of these receptors are excitatory, mediated by receptor-coupled ion channels. 5-HT3 antagonists (eg ondansetron, tropisetron) are used predominantly as anti-emetic drugs. 5-HT4 receptors are found in the brain, as well as peripheral organs like the heart, bladder and gastrointestinal (GI) tract. Within the GI tract they produce neuronal excitation and mediate the effect of 5-HT in stimulating peristalsis. A specific 5-HT4 agonist is metoclopramide used for treating gastrointestinal disorders. Little is known about the function and pharmacology of 5-HT5, 5-HT6 and 5-HT7 receptors.
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References
Other peripheral mediators: 5-hydroxytryptamine and purines. In: Pharmacology, 4th edition. Rang HP, Dale MM and Ritter JM. Edinburgh, UK: Harcourt Publishers Ltd, 2001:164–176.