5-hydroxytryptamine receptor 3 (5-HT3) (5-HT3)

The 5-hydroxytryptamine receptor 3 (5-HT3) is a member of the Cys-loop superfamily of ligand-gated ion channels, distinguishing it from all other serotonin receptors which are G protein-coupled receptors (IUPHAR/BPS Guide to Pharmacology, 2024). It is composed of five subunits (HTR3A-E) that form a central pore permeable to sodium, potassium, and calcium ions (UniProt, P46098). In the human body, these receptors are highly expressed in the area postrema of the brainstem and on the vagus nerve terminals in the gastrointestinal tract (StatPearls, 2023). Activation of 5-HT3 receptors by serotonin triggers the emetic reflex and modulates intestinal motility and fluid secretion (Thompson and Lummis, 2007). Consequently, 5-HT3 receptor antagonists like ondansetron are widely used to prevent chemotherapy-induced and postoperative nausea and vomiting (NCI, 2023). Beyond emesis, the receptor is a target for treating diarrhea-predominant irritable bowel syndrome with drugs like alosetron (FDA, 2022). Emerging research also explores its role in psychiatric conditions, including anxiety and cognitive impairment, due to its influence on neurotransmitter release in the forebrain (PubMed, 2014).

Other names

Serotonin receptor 3HTR35-HT3 receptor5-hydroxytryptamine receptor 3 complex5-HT3R

Antagonism of the ligand-gated ion channel to inhibit excitatory neurotransmission and vagal signaling (StatPearls, 2023).