Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorders: alterations in 5-HT signalling and metabolism in human disease.
Serotonin (5-hydroxytryptamine, 5-HT) is present in abundance within the gut, most stored in enterochromaffin cell granules. It is released by a range of stimuli, most potently by mucosal stroking. Released 5-HT stimulates local enteric nervous reflexes to initiate secretion and propulsive motility. It also acts on vagal afferents altering motility and in large amounts induces nausea. Rapid reuptake by a specific transporter (serotonin transporter, SERT) limits its diffusion and actions. Abnormally increased 5-HT is found in a range of gastrointestinal disorders including chemotherapy-induced nausea and vomiting, carcinoid syndrome, coeliac disease, inflammatory bowel disease and irritable bowel syndrome (IBS) with diarrhoea (IBS-D), especially that developing following enteric infection. Impaired SERT has been described in IBS-D and might account for some of the increase in mucosal 5-HT availability. 5-HT(3) receptor antagonists inhibit chemotherapy-induced nausea and diarrhoea associated with both carcinoid syndrome and IBS. While IBS-D is associated with increased 5-HT postprandially, IBS with constipation (IBS-C) is associated with impaired 5-HT response and responds to 5-HT(4) agonists such as Prucalopride and 5-HT(4) partial agonists such as Tegaserod.
Spiller
R
R
Professor of Gastroenterology, Wolfson Digestive Diseases Centre, Nottingham, UK. robin.spiller@nottingham.ac.uk
D000970:Antineoplastic Agents / Q000009:adverse effects; D002169:Campylobacter Infections / Q000378:metabolism; D002446:Celiac Disease / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects; D003109:Colonic Diseases, Functional / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000378:metabolism; D008303:Malignant Carcinoid Syndrome / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D000970:Antineoplastic Agents; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D002945:Cisplatin