Irritable bowel syndrome (IBS) is a highly prevalent disorder, the pathophysiology of which, until recently, was poorly understood. Research advances have identified serotonin signaling abnormalities as a possible cause. The role of serotonin in the enteric nervous system (ENS)the primary control center of gut functionwas reviewed by Michael Gershon, MD, in the Journal of Clinical Gastroenterology (May/June 2005). Among the key points discussed were the essential roles of enterochromaffin cells, serotonin, and intrinsic primary afferent neurons (IPANs) in receiving and transmitting signals within the gut. Enterochromaffin cells act as sensory transducers, communicating conditions in the bowel by releasing the neurotransmitter serotonin (5- hydroxytryptamine [5-HT]).
When released, serotonin binds to the 5-HT1b receptor on submucosal IPANs, resulting in the release of neurotransmitters that initiate peristaltic and secretory reflexes. Subsequent binding of serotonin to 5-HT4 receptors enhances the release and potentiates the effects of these neurotransmitters, augmenting peristalsis. Conversely, stimulation of the 5-HT3 receptor activates the extrinsic visceral afferent neurons, thereby affecting visceral sensation. The distinct roles and clear segregation of these serotonin receptor subtypes in the gut have led to the development of medications that manipulate serotonergic signaling in the ENS.