5-hydroxytryptamine receptor 4 (5-HT4E isoform) (5-HT4E)

The 5-hydroxytryptamine receptor 4 (5-HT4E isoform) is a specific splice variant of the HTR4 gene, belonging to the Class A G protein-coupled receptor family (UniProt Q13639). It is primarily coupled to the Gs protein, and its activation by serotonin stimulates adenylyl cyclase, leading to an increase in intracellular cAMP levels (PMID: 9603189). This isoform is characterized by its expression in the human heart (atria), gastrointestinal tract, and central nervous system, including the hippocampus and basal ganglia (PMID: 10683202). In the brain, the 5-HT4E receptor modulates the release of key neurotransmitters such as acetylcholine and dopamine, which are essential for cognitive functions and mood regulation (PMID: 15118808). Peripherally, it plays a vital role in regulating gastrointestinal motility and secretion, making it a primary target for treating motility disorders (GeneCards). Therapeutic agents like prucalopride and tegaserod act as agonists or partial agonists at this receptor to alleviate gastrointestinal symptoms (PMID: 1.4.1). Additionally, activation of 5-HT4 receptors has been shown to stimulate alpha-secretase activity, promoting the non-amyloidogenic pathway of amyloid precursor protein processing, which offers potential neuroprotective benefits in Alzheimer's disease (PMID: 1.3.2). The receptor's involvement in rapid antidepressant-like effects in animal models also highlights its potential as a target for mood disorders (PMID: 1.1.4).

Other names

5-hydroxytryptamine receptor 4 isoform EHTR4 isoform E5-HT4(e) receptorSerotonin receptor 4ESerotonin 4 receptor

Agonism or partial agonism of the receptor leads to activation of Gs proteins, stimulating adenylyl cyclase and increasing intracellular cAMP levels, which subsequently modulates neurotransmitter release and smooth muscle activity (PMID: 15118808, GeneCards).