5-hydroxytryptamine receptor 4 isoform e (5-HT4e)

The 5-hydroxytryptamine receptor 4 isoform e (5-HT4e) is a specific splice variant of the 5-HT4 receptor, which belongs to the G protein-coupled receptor (GPCR) superfamily. This isoform is distinguished by its unique C-terminal tail, which is produced through alternative splicing of the HTR4 gene and mediates specific interactions with intracellular proteins like nNOS and PATJ. Like other 5-HT4 receptors, the 4e isoform is positively coupled to the Gs protein, leading to the activation of adenylate cyclase and an increase in intracellular cyclic AMP (cAMP). This signaling cascade facilitates the release of various neurotransmitters, including acetylcholine and serotonin, thereby modulating functions such as gastrointestinal motility, memory, and mood. The 5-HT4 receptor is a well-established therapeutic target for gastrointestinal disorders, including irritable bowel syndrome (IBS) and chronic constipation, where agonists like prucalopride are used to enhance motility. It is also being investigated as a target for cognitive enhancement in Alzheimer's disease and for its rapid-acting antidepressant effects. However, the clinical use of 5-HT4 modulators is often limited by safety concerns, particularly cardiovascular risks such as arrhythmias and ischemic events associated with certain agonists.

Other names

HTR4 isoform eSerotonin receptor 4e5-HT4(e) receptor5-hydroxytryptamine receptor 4e

Agonists bind to the receptor and activate Gs-protein signaling, which stimulates adenylate cyclase to increase intracellular cAMP levels, leading to enhanced neurotransmitter release and smooth muscle modulation.