Involvement of 5-hydroxytryptamine (5-HT) in the survival and proliferation of Interstitial cells of Cajal (ICC)

Several human motility disorders such as chronic intestinal pseudo obstruction and slow transit constipation are associated with a decreased number of Interstitial cells of Cajal (ICC). Mutations in the tyrosine kinase receptor, c-Kit (W/Wv mice), or its ligand, Steel factor (Sl/Sld mice), have shown that the c-Kit-Steel factor signaling pathway is important to the survival and maintenance of ICC. The aim of this project is to determine whether other survival and growth factors also modulate ICC numbers.

In the gastrointestinal tract, 5-HT plays a significant role in the regulation of motility functioning as both a neurotransmitter and a paracrine modulator. Increasing evidence also suggests that 5-HT plays a role in regulating cellular growth, differentiation, and survival of diverse cell types. Preliminary studies have demonstrated that 5-HT alters ICC number in primary cell cultures. Further experiments are being carried out to identify diverse 5-HT receptors on ICC and their potential involvement in ICC survival and proliferation.

Selected Publications (Complete list of publications)

• Wouters MM, Gibbons SJ, Roeder JL, Distad M, Ou Y, Strege PR, Szurszewski JH, Farrugia G. Exogenous serotonin regulates proliferation of interstitial cells of Cajal in mouse jejunum through 5-HT2B receptors. Gastroenterology. 2007 Sep;133(3):897-906.