Characterization of melatonin receptors and their signal transduction in the epithelia

grantor: University of TorontoSpecific 2- ($\sp{125}$I) iodomelatonin binding sites have been observed in various peripheral tissues, including kidney and intestine. Such findings suggest the existence of epithelial melatonin receptors which implies that melatonin may exert certain epithelial functions. To investigate putative epithelial melatonin function, initially a study was carried to determine the subcellular distribution of melatonin receptors (MR) in the guinea pig small intestinal epithelia. To study the cellular mechanism of melatonin action on epithelia in greater detail, putative in vitro model systems including MDCK-1, LLPCK-1, OK-3, Caco-2 and HEK-293 (HEK) cells were tested for the presence of MR using 2- ($\sp{125}$I) iodomelatonin radioligand receptor binding. To explore the molecular and cellular mechanisms of melatonin action on epithelia, the effects of melatonin on cAMP were examined. Along with the characterization of the MR in intestinal BLM and HEK cells, this study has also established the HEK cells as a useful in vitro model system and investigated the differential effects of melatonin on hormonal stimulated cAMP levels. (Abstract shortened by UMI.)M.Sc