Role of 5-Hydroxytryptamine in the control of gut motility

By far the largest quantity of serotonin (5-hydroxytryptamine, 5-HT) that is found in the body is synthesized within the mucosal lining of the gut wall, in specialized cells called enterochromaffin (EC) cells, via the enzyme tryptophan hydroxylase-1 (TPH1). On a much smaller scale, 5-HT is also synthesized in approximately 1% of nerve cells bodies in the enteric nervous system (ENS), via a different enzyme called tryptophan hydroxylase-2. Because such high quantities of 5-HT are synthesized within the gut wall, there have been many studies over the past century that have been directed to understanding the functional role of 5-HT, particularly with regards to the different motor patterns in the gastrointestinal (GI) tract. Since the early 1950s there has been gathering evidence to support a compelling case that 5-HT released from the gut wall played an important role in the generation and/or modulation of propagating neurogenic motor patterns along the GI tract, particularly the small and large intestine. It is important to acknowledge that the corresponding author of this review was also convinced and had published that endogenous 5-HT, synthesized within the gut wall likely had a major influence in the generation of GI motor patterns, particularly in the small and large intestines. However, over the past 10-15 years, with the advent of functional genomics and development of precise molecular techniques to genetically ablate specific genes of interest, there have been some startling and unexpected changes in our understanding of the role of endogenous 5-HT in GI motility and transit. This review will highlight the existing doctrine regarding the role of endogenous 5-HT in GI motility, then contrast how these views have been revised in recent years, as new more refined techniques have emerged.