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Serotonin (5-HT) has extensively been studied in the central and enteric nervous system. Altered levels of 5-HT play a role in many central nervous system (CNS) disorders and can be treated with specific 5-HT receptor agonists and antagonists. Interestingly, 95% of the bodies 5-HT is located outside central neuronal regions and in the intestine. The discovery of 5-HT secreting cells in the intestinal epithelium has resulted in a fruitful area of research that is focused on the function of intestinal epithelium-derived 5-HT.1 The subsequent discovery that 5-HT may play an important role in driving intestinal inflammation has generated interest in the potential of 5-HT antagonists for treatment of inflammatory bowel disease (IBD). However, side effects related to the important role of 5-HT in the enteric and central nervous system have precluded drug development in this field. In this issue of Gut, Margolis et al2 use mouse models to demonstrate that it may be possible to selectively inhibit intestinal mucosal 5-HT signalling and suppress intestinal inflammation without such side effects.
In the intestine, 5-HT is produced by a subset of enteroendrocrine cells called enterochromaffin …