5-Hydroxytryptamine 2B receptor (IPR000482)
Short name: 5HT2B_rcpt
Overlapping homologous superfamilies
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 5-HT2B receptor has been shown to be distributed in a range of tissues, including human gut, brain and the cardiovascular system [PMID: 8706927, PMID: 8078486, PMID: 8078486, PMID: 1331748]. In the cardiovascular system the 5-HT2B receptor regulates cardiac structure and function [PMID: 11413089]. 5-HT2B receptor stimulation can also lead to pathological proliferation of cardiac valve fibroblasts [PMID: 18511249], which, with chronic overstimulation, can lead to a severe valvulopathy. In addition, the 5-HT2B receptor has been shown to be involved in pulmonary hypertension via vasoconstriction [PMID: 12244304]. As a result 5-HT2B antagonists have been developed as treatments for chronic heart disease [PMID: 19118279, PMID: 19307114]. In the CNS the 5-HT2B receptor has been shown to be involved in presynaptic inhibition, leading to behavioural effects [PMID: 18337424], since it is important to the normal regulation of serotonin levels in the blood plasma [PMID: 16461587] and abnormal release produced by drugs such as MDMA [PMID: 18337424].
GO:0004993 G protein-coupled serotonin receptor activity
GO:0016021 integral component of membrane