5-hydroxytryptamine receptor 3 (5-HT3) and 5-hydroxytryptamine receptor 4 (5-HT4) (5-HT3/4)

The 5-hydroxytryptamine (5-HT) system, specifically the 5-HT3 and 5-HT4 receptors, plays a critical role in regulating gastrointestinal (GI) function and the central nervous system (IUPHAR/BPS Guide to Pharmacology, 2024). The 5-HT3 receptor is a unique member of the serotonin receptor family as it is a ligand-gated ion channel, primarily responsible for rapid excitatory neurotransmission and the mediation of the emetic reflex (UniProt P46098). In contrast, the 5-HT4 receptor is a G protein-coupled receptor that stimulates adenylyl cyclase, leading to increased acetylcholine release and enhanced GI motility (UniProt Q13639). These receptors are major therapeutic targets for managing GI disorders; 5-HT3 antagonists like ondansetron are gold-standard treatments for chemotherapy-induced nausea and vomiting (StatPearls, 2023). 5-HT4 agonists like prucalopride are used as prokinetic agents for chronic constipation and irritable bowel syndrome (PubMed, 2022). Pharmacological modulation of these receptors requires careful management due to potential side effects, including QT prolongation and cardiovascular risks (FDA, 2020). Together, these receptors represent distinct but complementary pathways for controlling enteric nervous system activity and visceral sensation.

Other names

Serotonin receptor 3Serotonin receptor 4HTR3HTR45-HT3R5-HT4R5-hydroxytryptamine system

5-HT3 receptor antagonism (blocking ligand-gated cation channels on vagal afferents) and 5-HT4 receptor agonism (stimulating Gs-coupled receptors to increase cAMP and acetylcholine release in the enteric nervous system).