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 (I(SC)) technique. Basolateral, as well as apical, addition of melatonin stimulated I(SC) in a concentration-dependent manner (EC50 at about 100 microM). 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 Gi-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 Cl- secretion via melatonin receptors; however, the signal transduction pathway(s) involved remains to be elucidated.
Chan
H C
HC
Department of Physiology, The Chinese University of Hong Kong, Shatin. hsiaocchan@cuhk.edu.hk
Lui
K M
KM
Wong
W S
WS
Poon
A M
AM
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006801:Humans; D007097:Imines / Q000494:pharmacology; D008550:Melatonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D044094:Receptors, Melatonin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D002121:Calcium Channel Blockers; D018118:Chloride Channels; D002712:Chlorides; D007097:Imines; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D010566:Virulence Factors, Bordetella; D062367:ortho-Aminobenzoates; C014925:RMI 12330A; C044556:2-iodomelatonin; C001209:fenamic acid; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000262:Adenylyl Cyclases; D008550:Melatonin; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; C012365:6-hydroxymelatonin