5-hydroxytryptamine receptor 4 (5-HT4 receptor) (5-HT4R)

The 5-hydroxytryptamine receptor 4 (5-HT4 receptor) is a G protein-coupled receptor (GPCR) that plays a pivotal role in the regulation of gastrointestinal (GI) motility and cognitive functions (Source: UniProt P47811). It is primarily coupled to the Gs protein, which stimulates adenylyl cyclase to increase intracellular cyclic AMP (cAMP) levels, thereby modulating the release of various neurotransmitters such as acetylcholine and serotonin (Source: IUPHAR/BPS Guide to Pharmacology). In the GI tract, 5-HT4 receptors are located on enteric neurons and smooth muscle cells, where their activation promotes the peristaltic reflex and intestinal secretion, making them primary targets for treating chronic constipation and irritable bowel syndrome with constipation (IBS-C) (Source: PMID: 21559239). Beyond the gut, these receptors are expressed in the central nervous system, particularly in the hippocampus and cortex, where they contribute to memory formation and learning processes (Source: PMID: 11511161). Therapeutic development has focused on selective agonists like prucalopride to enhance GI transit, though historical concerns regarding cardiovascular safety—such as those seen with tegaserod—remain a critical consideration in drug design (Source: StatPearls).

Other names

HTR4Serotonin receptor 45-HT4 receptor5-hydroxytryptamine receptor 4

Agonists bind to the 5-HT4 receptor to activate the Gs-adenylyl cyclase pathway, leading to increased intracellular cAMP and subsequent release of neurotransmitters like acetylcholine, which enhances gastrointestinal motility and prokinetic activity (Source: IUPHAR/BPS Guide to Pharmacology).