5-Hydroxytryptamine receptor 4 (5-HT4 receptor)

The 5-Hydroxytryptamine receptor 4 (5‑HT₄ receptor) is a member of the serotonin GPCR family encoded by the HTR4 gene in humans. It is primarily expressed in both central and peripheral tissues including regions of the brain involved in motor control and cognition as well as throughout the gastrointestinal tract where it regulates motility. Activation by serotonin stimulates adenylate cyclase via Gs proteins leading to increased cAMP levels. The physiological roles include modulation of neurotransmitter release—affecting memory, learning, mood—and regulation of smooth muscle contraction especially within the GI tract. Pharmacologically important as a therapeutic target for prokinetic agents used in treating GI motility disorders; however safety issues such as cardiac arrhythmias have limited clinical use for some drugs targeting this pathway.

Other names

HTR45-HT4Serotonin receptor 45-hydroxytryptamine receptor 4

Drugs targeting the 5-Hydroxytryptamine receptor 4 typically act as agonists that stimulate the receptor to increase cyclic AMP production via Gs protein coupling. This leads to enhanced peristalsis in the gut, increased gastric emptying, and modulation of neurotransmitter release in the central nervous system. Antagonists block these effects.