Serotonin receptor subtype 4 (5-HT4 receptor)

Serotonin receptor subtype 4 (5-HT4 receptor, HTR4) is a G protein-coupled receptor predominantly coupled to Gs proteins, leading to the stimulation of adenylyl cyclase and increased intracellular cAMP[4][6][7]. It is structurally defined by seven transmembrane domains typical of class A (rhodopsin-like) GPCRs and exists in several splice variants with tissue-dependent expression, especially in the gastrointestinal tract, heart, and brain[4]. The 5-HT4 receptor plays a crucial physiological role in facilitating gastrointestinal motility by enhancing neurotransmitter release in the enteric nervous system, as well as modulating cardiac contractility and certain neuronal functions related to memory and cognition[4][6][7]. Clinically, it serves as a therapeutic target for gastrointestinal disorders such as irritable bowel syndrome and chronic constipation, but its role in cardiac tissue raises safety concerns regarding arrhythmogenic risk for certain agonists (notably cisapride and tegaserod)[4].

Other names

5-hydroxytryptamine receptor 45-HT4RHTR4

Agonists enhance gastrointestinal peristalsis by stimulating cAMP production in enteric neurons Some antagonists block downstream cAMP signaling Agonists can enhance acetylcholine release in specific CNS and peripheral tissues