Serotonin and GI Disorders: An Update on Clinical and Experimental Studies

Abstract

The gastrointestinal (GI) tract is the largest producer of serotonin (5-hydroxytryptamine (5-HT)) in the body, and as such it is intimately connected with GI function and physiology. 5-HT produced by enterochromaffin (EC) cells is an important enteric mucosal signaling molecule and has been implicated in a number of GI diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. This review will focus on what is known of basic 5-HT physiology and also on the emerging evidence for its novel role in activation of immune response and inflammation in the gut. Utilizing pubmed.gov, search terms such as "5-HT," "EC cell," and "colitis," as well as pertinent reviews, were used to develop a brief overview of EC cell biology and the association between 5-HT and various GI disorders. It is the aim of this review to provide the readers with an update on EC cell biology and current understanding on the role of 5-HT in GI disorders specifically in inflammatory conditions.

Figure 1

Modulation of EC cell biology by immune cells and modulation of immune cells by 5-HT in GI disease. The role of 5-HT in modulating the innate and adaptive immune system can vary by cell type. 5-HT has been shown to enhance phagocytosis in murine macrophages. In addition, 5-HT can increase chemotaxis of dendritic cells and promote the release of the Th2-attracting chemokine CCL22 while decreasing the Th1 chemokine CXCL10. Finally 5-HT has a proliferative effect on CD4+ T cells, which when coupled with 5-HT effect on dendritic cells create a more permissive environment for a Th2 immune response. CD4+ T cells particularly Th2 cytokines, such as interleukin-13, in turn may influence on EC cell biology, 5-HT synthesis, and 5-HT release.