5-Hydroxytryptamine 2A receptor (IPR000455)

Short name: 5HT2A_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].

This entry represents the 5-HT2A receptor (previously classified just as 5-HT2), which is one of the main excitatory serotonin receptors. It is expressed throughout the central nervous system [PMID: 9555012, PMID: 7796165] with high concentrations found on the apical dendrites of pyramidal cells in layer V of the cortex [PMID: 10216183, PMID: 11672605, PMID: 16277612], which are thought to modulate cognitive processes by enhancing glutamate release followed by a complex range of interactions with the 5-HT1A [PMID: 14754868], GABAA [PMID: 11517239], adenosine A1 [PMID: 19324062], AMPA [PMID: 17728034], mGluR2/3 [PMID: 11027922], mGlu5 [PMID: 18621097] and OX2 receptors [PMID: 2779889]. In the periphery, the 5-HT2A receptor is highly expressed in platelets and many cell types of the cardiovascular system, in fibroblasts, and in neurons of the peripheral nervous system. Additionally, 5-HT2A mRNA expression has been observed in human monocytes [PMID: 1580230], and platelet aggregation [PMID: 9491270] with increased capillary permeability following exposure to 5-HT have been attributed to 5-HT2A receptor-mediated functions. 5-HT2A receptors also mediate contractile responses in a series of vascular smooth muscle preparations [PMID: 11960784] and activation in hypothalamus causes increases in hormonal levels of oxytocin, prolactin, ACTH, corticosterone, and renin [PMID: 12417689].

GO terms

Biological Process

GO:0007186 G protein-coupled receptor signaling pathway

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.