Mucosal protection through active intestinal secretion: neural and paracrine modulation by 5-hydroxytryptamine

5-Hydroxytryptamine (5-HT) is widely distributed within enteroendocrine cells and neurons of the digestive tract. It stimulates active anion secretion in the intestinal epithelium, an effect which promotes the dilution and elimination of luminal pathogens. The intestinal secretory effects of 5-HT appear to be mediated in part by epithelial 5-HT₂ like receptors that are linked to phosphatidylinositol turnover. In addition, 5-HT appears to interact with 5-HT₃ or 5-HT₄ receptors on submucosal neurons to elicit neuronal depolarization and an associated increase in intestinal secretion. Although the precise cellular mechanisms by which 5-HT modulates mucosal ion transport are incompletely understood, it is clear that 5-HT plays an important role as a intestinal secretagogue in certain diarrheal states, in laxation, and in intestinal hypersensitivity reactions.