Review article: roles played by 5‐hydroxytryptamine in the physiology of the bowel

Abstract

The application of 5‐HT to the gut elicits a wide variety of effects because of the expression and wide distribution in the bowel of many subtypes of 5‐HT. There is, however, no reason to believe that all of these receptors are stimulated by endogenous 5‐HT. 5‐HT has been found to be the neurotransmitter of a subset of myenteric interneurons, which evoke a slow excitatory postsynaptic response mediated by 5‐HT 1P receptors. The major enteric depot of 5‐HT is found in mucosal enterochromaffin cells, which are sensory transducers that utilize 5‐HT to activate both intrinsic (via 5‐HT 1P and 5‐HT 4 receptors) and extrinsic (via 5‐HT 3 receptors) primary afferent nerves. Mucosal 5‐HT is inactivated by uptake into epithelial cells mediated by the same 5‐HT transporter utilized by serotonergic neurons. Antagonism of 5‐HT 3 receptors by compounds such as alosetron should be useful in treating functional bowel disease because they can inhibit excitation of extrinsic sensory nerves by 5‐HT without interfering with intrinsic enteric reflexes.