Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the gut, 5-HT acts as a paracrine signalling molecule released by enterochromaffin cells and as a transmitter released by some descending serotonergic interneurons. It has a prominent role in the regulation of motility, vascular tone, secretion and perception both in normal and under certain pathophysiological conditions, such as the carcinoid syndrome and the irritable bowel syndrome (IBS). Serotonin is known to markedly influence bowel function by activating at least five receptor types (5-HT(1,2,3,4,7)). Among all 5-HT receptors, those belonging to the 5-HT3 (a ionotropic receptor) and 5-HT4 (a metabotropic receptor) type are the most extensively studied in gastroenterology, resulting in commercially available (although not worldwide) serotonergic agents for the treatment of IBS and functional dyspepsia. Recently, 5-HT7 receptors have been found to participate in the accommodation process of the circular muscle during the preparatory phase of ileal peristalsis. Since an exaggerated accommodation of the gut wall may contribute to abdominal distension and bloating, 5-HT7 receptor ligands may offer innovative opportunities for the pharmacological treatment of functional bowel disorders.
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PMID:[Recent insights into the pathogenesis of abdominal symptoms in functional bowel disorders]. 1743 64

Researching the functions of serotonin, or 5-hydroxytryptamine (5-HT), in the gut has helped define new 5-HT receptors, increased the understanding of the side effects of numerous drugs and, via development of drugs, brought relief to millions of people suffering from disorders such as gastroparesis, dyspepsia, constipation, diarrhoea, irritable bowel syndrome and cancer. However, safety issues associated with alosetron and tegaserod (key drugs that modulate 5-HT function) have brought 5-HT and gastrointestinal research to a crossroad--is it now too hard to develop drugs in this area or is there a way forward? In this review, I describe the background to 5-HT in gastrointestinal physiology and disease, and the actions of drugs that interact with 5-HT3 and 5-HT4 receptors. Future research directions include modulating 5-HT availability by inhibition of tryptophan hydroxylase, understanding the functions of receptors such as 5-HT2B, 5-HT7 and the recently described 5-HT3-receptor subunits, and investigating how receptors activated by other products of tryptophan catabolism interact with gastrointestinal functions of 5-HT.
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PMID:5-hydroxytryptamine and the gastrointestinal tract: where next? 1908 55