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.
Gershon
M D
MD
Department of Anatomy & Cell Biology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA. mdg4@columbia.edu
D000818:Animals; D002243:Carbolines / Q000627:therapeutic use; D003109:Colonic Diseases, Functional / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007413:Intestinal Mucosa; D007422:Intestines / Q000294:innervation / Q000502:physiology*; D011985:Receptors, Serotonin; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000627:therapeutic use
D002243:Carbolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C090840:alosetron; D012701:Serotonin