5-Hydroxytryptamine 2C receptor (IPR000377)

Short name: 5HT2C_rcpt

Overlapping homologous superfamilies


Family relationships


5-hydroxytryptamine (5-HT) or serotonin, is a neurotransmitter that it is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS). It is implicated in a vast array of physiological and pathophysiological pathways. Receptors for 5-HT mediate both excitatory and inhibitory neurotransmission, and modulate the release of many neurotransmitters including glutamate, GABA, dopamine, epinephrine/norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin and cortisol. In the CNS, 5-HT receptors can influence various neurological processes, such as aggression, anxiety and appetite and, as a, result are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics and anorectics [PMID: 18476671].

The 5-HT receptors are grouped into a number of distinct subtypes, classified according to their antagonist susceptibilities and their affinities for 5-HT. With the exception of the 5-HT3 receptor, which is a ligand-gated ion channel [PMID: 11989819], all 5-HT receptors are members of the rhodopsin-like G protein-coupled receptor family [PMID: 18476671], and they activate an intracellular second messenger cascade to produce their responses.

The 5-HT2 receptors mediate many of the central and peripheral physiologic functions of 5-hydroxytryptamine. The original 5HT2 receptor (now renamed as the 5-HT2A receptor) was initially classified according to its ability to display micromolar affinity for 5-HT, to be labelled with [3H]spiperone and by its susceptibility to 5-HT antagonists. At least 3 members of the 5HT2 receptor subfamily exist (5-HT2A, 5-HT2B, 5-HT2C), all of which share a high degree of sequence similarity and couple to Gq/G11 to stimulate the phosphoinositide pathway and elevate cytosolic calcium. Cardiovascular effects include contraction of blood vessels and shape changes in platelets; central nervous system effects include neuronal sensitisation to tactile stimuli and mediation of some of the effects of phenylisopropylamine hallucinogens. 5-HT2 receptors display functional selectivity in which the same agonist in different cell types or different agonists in the same cell type can differentially activate multiple, distinct signalling pathways [PMID: 16803859].

The distribution of 5-HT2C is limited to the CNS and choroid plexus [PMID: 8028479]. Activation of the receptor has been shown to exert an inhibitory influence upon frontocortical dopaminergic and adrenergic, but not serotonergic transmission and, in part, to play a role in neuroendocrine function [PMID: 9776391, PMID: 10223282, PMID: 10503938, PMID: 15668911]. Additional characteristic behavioural responses attributed to 5-HT2C receptor activation include hypoactivity [PMID: 7912626, PMID: 9694950, PMID: 10219979], feeding [PMID: 7912626, PMID: 9694950, PMID: 10219979, PMID: 11489456, PMID: 11228755], reproductive behaviour [PMID: 9151932] and thermoregulation [PMID: 9106912]. Chronic treatment with antipsychotic drugs that are 5-HT2 antagonists results in downregulation of both 5-HT2A and 5-HT2C receptors, as does chronic treatment with SSRIs and 5-HT agonists [PMID: 11750789]. However, chronic SSRI treatment may increase 5-HT2C expression, specifically in the choroid plexus [PMID: 8840350].

GO terms

Biological Process

GO:0007186 G protein-coupled receptor signaling pathway
GO:0007631 feeding behavior
GO:0007626 locomotory behavior

Molecular Function

GO:0004993 G protein-coupled serotonin receptor activity

Cellular Component

GO:0005887 integral component of plasma membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.