5HT2B

The 5-HT2B receptor, also written as 5-HT2B or 5-hydroxytryptamine receptor 2B, is a subtype of serotonin receptor that belongs to the G protein-coupled receptor family. It is encoded by the HTR2B gene and is part of the 5-HT2 receptor group, which also includes 5-HT2A and 5-HT2C. In most tissues, 5-HT2B signals mainly through Gq/11 proteins to activate phospholipase C, leading to generation of IP3 and DAG and an increase in intracellular calcium; in some cell types it can couple to other G proteins and trigger additional signaling pathways.

Expression of 5-HT2B is notable in heart valve interstitial cells, various regions of the brain, vascular smooth muscle, and enteric neurons. Serotonin is the endogenous ligand, and a range of agonists and antagonists interact with 5-HT2B, though selectivity among 5-HT2 family members can be limited in older compounds.

Physiological roles attributed to 5-HT2B include modulation of cardiovascular function and connective tissue remodeling in the heart valves, as well as neuromodulatory effects in the central nervous system. In the heart, 5-HT2B signaling can promote valvular interstitial cell proliferation and extracellular matrix production, contributing to valvular remodeling under certain conditions. In the brain, 5-HT2B participates in circuits that influence mood and cognition, though its precise roles are less well defined than those of other serotonin receptors.

Clinical significance centers on drug safety: agonism at 5-HT2B has been linked to drug-induced valvular heart disease. Notable examples include the weight-loss drugs fenfluramine and dexfenfluramine and the ergot-derived dopamine agonist pergolide, which led to regulatory restrictions or withdrawal of such compounds. Conversely, 5-HT2B antagonists have been explored as potential therapies to prevent fibrosis and certain forms of pulmonary arterial hypertension, though no selective 5-HT2B antagonist is currently a standard treatment. The receptor remains a focus in pharmacology for understanding serotonin signaling and cardiovascular safety in drug development.