5-hydroxytryptamine receptor 4 isoform B (5-HT4B)

The 5-hydroxytryptamine receptor 4 isoform B (5-HT4B) is a specific splice variant of the 5-HT4 receptor, a member of the G protein-coupled receptor (GPCR) superfamily (UniProt, https://www.uniprot.org/uniprotkb/Q13639/entry). It is primarily coupled to the Gs protein, which stimulates adenylate cyclase to increase intracellular cyclic AMP (cAMP) levels, thereby modulating various physiological processes (PubMed, https://pubmed.ncbi.nlm.nih.gov/16102731/). 5-HT4B is widely expressed in the central nervous system, particularly in the basal ganglia and hippocampus, and is the dominant isoform in the human heart and gastrointestinal tract (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266613/). In the gut, its activation promotes peristalsis and secretion, making it a key target for prokinetic drugs used in treating chronic constipation and irritable bowel syndrome (Wikipedia, https://en.wikipedia.org/wiki/5-HT4_receptor). In the brain, it facilitates the release of neurotransmitters such as acetylcholine and dopamine, suggesting therapeutic potential for cognitive disorders like Alzheimer's disease and mood disorders like depression (MDPI, https://www.mdpi.com/1422-0067/24/13/10462). However, its presence in the heart is associated with risks of atrial arrhythmias, and historical non-selective agonists have faced regulatory restrictions due to cardiovascular safety concerns (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306208/).

Other names

HTR4BSerotonin receptor 4 isoform B5-HT4(b)HTR4

Agonists bind to the 5-HT4B receptor, activating Gs proteins that stimulate adenylate cyclase to increase intracellular cyclic AMP (cAMP) levels. This second messenger cascade enhances the release of neurotransmitters (e.g., acetylcholine) and promotes smooth muscle contraction in the gastrointestinal tract. Antagonists competitively inhibit this receptor to reduce excessive motility or cardiac excitability.