5-hydroxytryptamine receptor 2B (5-HT2B) (5-HT2B)

The 5-hydroxytryptamine receptor 2B (5-HT2B) is a G protein-coupled receptor (GPCR) that mediates various physiological responses to serotonin (5-HT) (UniProt P41595). It is widely expressed in the cardiovascular system, gastrointestinal tract, and brain, where it regulates smooth muscle contraction, vascular tone, and embryonic heart development (NCBI Gene ID: 3357). In clinical pharmacology, the 5-HT2B receptor is most significant as an "anti-target" due to its role in drug-induced valvular heart disease (VHD) (PubMed PMID: 10742028). Chronic activation of this receptor on cardiac valvular interstitial cells promotes fibroblast proliferation and extracellular matrix deposition, leading to valve thickening and dysfunction (PubMed PMID: 15833718). This mechanism led to the withdrawal of several drugs, such as fenfluramine and pergolide, from the market (StatPearls: Serotonin Syndrome). Consequently, 5-HT2B receptor affinity screening is a critical safety component in the development of new serotonergic medications (IUPHAR/BPS Guide to Pharmacology). While antagonists have been investigated for treating conditions like migraine and irritable bowel syndrome, the receptor's primary clinical relevance remains its association with severe cardiotoxicity (PubMed PMID: 10742028). The receptor primarily couples to Gq/11 proteins to activate the phospholipase C signaling pathway, and it also plays a role in platelet shape change and enteric nervous system function (UniProt P41595; IUPHAR/BPS Guide to Pharmacology).

Other names

HTR2BSerotonin receptor 2B5-HT-2B receptor5-hydroxytryptamine receptor 2B

Agonism and Antagonism