Review Article: Intestinal Serotonin Signalling in Irritable Bowel Syndrome

G. M. Mawe; M. D. Coates; P. L. Moses

Disclosures

Aliment Pharmacol Ther. 2006;23(8):1067-1076. 

In This Article

Editor's Note

Please note: The following announcement supersedes any information contained in this article. On March 30, 2007, Novartis, in compliance with an FDA request, suspended marketing and sales of its irritable bowel/constipation drug tegaserod maleate (Zelnorm) after an analysis of its clinical database pointed to a higher incidence of myocardial infarction, stroke, and unstable angina among patients taking the drug. For updated information on this issue, see the Medscape Alert Center on tegaserod.

 

Summary and Introduction

 

 

 

Summary

Alterations in motility, secretion and visceral sensation are hallmarks of irritable bowel syndrome. As all of these aspects of gastrointestinal function involve serotonin signalling between enterochromaffin cells and sensory nerve fibres in the mucosal layer of the gut, potential alterations in mucosal serotonin signalling have been explored as a possible mechanism of altered function and sensation in irritable bowel syndrome. Literature related to intestinal serotonin signalling in normal and pathophysiological conditions has been searched and summarized.

Elements of serotonin signalling that are altered in irritable bowel syndrome include: enterochromaffin cell numbers, serotonin content, tryptophan hydroxylase message levels, 5-hydroxyindoleacedic acid levels, serum serotonin levels and expression of the serotonin-selective reuptake transporter. Both genetic and epigenetic factors could contribute to decreased serotonin-selective reuptake transporter in irritable bowel syndrome. A serotonin-selective reuptake transporter gene promoter polymorphism may cause a genetic predisposition, and inflammatory mediators can induce serotonin-selective reuptake transporter downregulation.

While a psychiatric co-morbidity exists with IBS, changes in mucosal serotonin handling support the concept that there is a gastrointestinal component to the aetiology of irritable bowel syndrome. Additional studies will be required to gain a more complete understanding of changes in serotonin signalling that are occurring, their cause and effect relationship, and which of these changes have pathophysiological consequences.

Introduction

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder associated with alterations in motility, secretion and visceral sensation. A range of clinical symptoms characterize this disorder, including altered stool frequency and form, abdominal pain and bloating. Impairment in quality of life is common for the significant proportion of the population who suffer from IBS.[1,2,3] Specific clinical criteria differentiate IBS from other functional GI disorders as well as from inflammatory bowel disease (IBD) and other non-functional GI disorders. There are no specific biological, radiographic, endoscopic or physiological markers that have been identified in this disorder, and therefore, the diagnosis of IBS is based solely on these clinical criteria. Despite extensive interest and investigation, the pathogenesis of IBS remains unclear. Improved understanding of the enteric nervous system (ENS), and the neuroenteric pathways involved in GI function, may provide a conceptual framework to integrate previously described motility, sensory, and cognitive features of the disease and to identify new therapeutic targets. In this article, we will specifically review the evolving understanding of the important roles of serotonin (5-HT) as a signalling molecule in the gut and the pathophysiology of functional GI disorders like IBS. We have searched and summarized relevant literature related to 5-HT signalling in the mucosa of the intestines under normal conditions and changes in key elements of 5-HT signalling that have been reported in IBS and in response to inflammation.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....