Effect of melatonin on chloride secretion by human colonic T84 cells

The effect of melatonin on human colonic T84 cells was studied using the short-circuit current (Isc) technique. Basolateral, as well as apical, addition of melatonin stimulated I-SC in a concentration-dependent manner (EC50 at about 100 mu M) The I-SC response to melatonin was nearly abolished when external Cl- was removed. The increase in I-SC was also blocked by apical addition of two Cl- channel blockers, 4,4'-diisothiocyanatostibene-2,2-'disulfonic acid (DIDS) and diphenylamine-2-carboxylic acid (DPC), indicating that melatonin stimulated Cl- secretion. The effect of different melatonin analogs was compared and the order of potency appeared to be 2-iodomelatonin > melatonin > 6-hydroxymelatonin, indicating the involvement of melatonin receptors. However, inhibitors for G(i)-protein, adenylate cyclase or phospholipase C were found to be ineffective in inhibiting the melatonin-induced I-SC Pretreatment of the cells with melatonin was also found to exert little effect on subsequent forskolin-or VIP-induced I-SC, further excluding its interaction with adenylate cyclase. Our data suggest that melatonin may play a role in regulating colonic CI secretion via melatonin receptors; however, the signal transduction pathway(s) involved remains to be elucidated.