Review Article: Roles Played by 5-hydroxytryptamine in the Physiology of the Bowel

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-HT1P 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-HT1P and 5-HT4 receptors) and extrinsic (via 5-HT3 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-HT3 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.