P314 Understanding the role of melatonin on colonic function

Introduction Melatonin is synthesized from 5-HT by the enzyme hydroxyindole-O-methyltransferase and the EC cells maybe a site of synthesis and release of mucosal melatonin. Although the presence of melatonin in the gastrointestinal tract is not disputed its role in regulating gastrointestinal motility and its mechanism of action are still debated. Methods We used electrochemical and chromatographic methods to detect the regulation of mucosal melatonin release from intact segments of 3 month old C57BL/6 murine colon. Colonic migratory motor complexes (CMMC) were recorded in the presence of melatonin, MT2 receptor antagonist 4-P-PDOT and MT1/2 receptor antagonist luzindole. Functional bioassays were carried out to study how varying concentrations of melatonin influenced electrical field stimulated (EFS) colonic contractions. The influence of melatonin on feacal pellet was explored. Results Melatonin release was shown to 2-fold greater than serotonin, when released from the colon (n=6). Melatonin release occurred on demand during mechanical stimulation but was not released by a chemical stimulus, the bile salt deoxycholic acid. EFS of isolated colon segments caused contraction at lower frequencies but relaxation at higher frequencies. In the proximal colon, 5 µM melatonin facilitated contraction at all EFS frequencies (p Conclusions Our findings highlight that melatonin is present and released from the colonic mucosa and has an important functional role in influencing muscle contraction. Therefore, melatonin signalling pathways may serve to be important targets to direct therapeutic development.