EFFECT OF MELATONIN ON CHLORIDE SECRETION BY HUMAN COLONIC T-84 CELLS

The effect of melatonin on human colonic T84 cells was studied using t he short-circuit current (Isc) technique. Basolateral, as well as apic al, addition of melatonin stimulated I-SC in a concentration-dependent manner (EC50 at about 100 mu M) The I-SC response to melatonin was ne arly abolished when external Cl- was removed. The increase in I-SC was also blocked by apical addition of two Cl- channel blockers, 4,4'-dii sothiocyanatostibene-2,2-'disulfonic acid (DIDS) and diphenylamine-2-c arboxylic acid (DPC), indicating that melatonin stimulated Cl- secreti on. The effect of different melatonin analogs was compared and the ord er of potency appeared to be 2-iodomelatonin > melatonin > 6-hydroxyme latonin, indicating the involvement of melatonin receptors. However, i nhibitors for G(i)-protein, adenylate cyclase or phospholipase C were found to be ineffective in inhibiting the melatonin-induced I-SC Pretr eatment of the cells with melatonin was also found to exert little eff ect on subsequent forskolin-or VIP-induced I-SC, further excluding its interaction with adenylate cyclase. Our data suggest that melatonin m ay play a role in regulating colonic CI secretion via melatonin recept ors; however, the signal transduction pathway(s) involved remains to b e elucidated.