5-HT₃ Receptor

5-HT₃ receptor is a serotonin-gated, cation-selective Cys-loop ligand-gated ion channel in the central and peripheral nervous systems^[1]. Mechanistically, ligand binding triggers conformational changes around the orthosteric binding site and opens an intrinsic cation-selective channel that supports fast serotonergic neurotransmission^[2]. Functional receptors require at least one 5-HT_3A subunit, while 5-HT_3B-5-HT_3E subunits assemble with 5-HT_3A and mainly modify receptor expression, conductance, or biophysical behavior^[3]. Compared with other serotonin receptor families, 5-HT₃ receptors are ion channels rather than G-protein-coupled receptors, which makes them distinct pharmacological and electrophysiological targets^[4]. In disease-relevant research, selective 5-HT₃ receptor antagonists are established for chemotherapy-induced and postoperative nausea and vomiting, and clinical use also includes irritable bowel syndrome^[1][4]. In sensory models, rat dorsal root ganglion neurons express functional 5-HT₃ receptors, and agonist-evoked Ca²⁺ influx can increase neurotransmitter release from DRG to spinal neurons^[5]. For experimental applications, agonists, competitive antagonists, and allosteric modulators help define ligand binding, channel gating, and subunit-dependent receptor function^[2][6].