In the gut,
serotonin (
5-hydroxytryptamine: 5-HT) exerts a variety of effects on intrinsic enteric neurons, extrinsic afferents, enterocytes and smooth muscle cells, which are related to the expression of multiple
5-HT receptor types and subtypes regulating motility, vascular tone, secretion and perception. Agonists and antagonists at
5-HT receptors have gained access to the market for the two major variants of the
irritable bowel syndrome (IBS), a functional disorder characterized by
abdominal pain associated with
diarrhea and/or
constipation in the absence of any organic abnormality. Indeed, the
5-HT3 receptor antagonist
alosetron is available in the US market for the treatment of women with severe,
diarrhea-predominant IBS (D-IBS) refractory to conventional
therapy, whereas
tegaserod, a partial
5-HT4 receptor agonist, has been approved by the FDA and other regulatory agencies for the treatment of women with
constipation-predominant IBS (C-IBS) or functional
constipation. This review is mainly intended to discuss the role of non-neuronal (paracrine) and neuronal
5-HT in the pathophysiology of
functional gastrointestinal disorders (FGIDs), such as IBS and functional
dyspepsia, and the mechanisms through which drugs acting on
5-HT receptors regulate visceral motility, perception and secretion in these two conditions.