[The role of thiol oxidants in inhibition of pancreatic exocrine secretory function and glutathione].
OBJECTIVE
Glutathione depletion has been described in all form of acute pancreatitis. This study evaluated the effect of glutathione depletion on pancreatic exocrine secretory function and explored the potential mechanisms.


METHODS
Thiol oxidants ethacrynic acid and diamide were employed to deplete pancreatic acinar glutathione. The effect of glutathione depletion on caerulein-stimulated amylase release, cholecystokinin (CCK) receptor binding characteristics, and cytosolic free calcium was investigated.


RESULTS
Both the thiol oxidants decreased the level of pancreatic acinar glutathione and caerulein (1 x 10(-10) mol/L)-stimulated amylase release in a dose-dependent manner without a marked increase in cell damage. Diamide also diminished the level of protein thiols. Ethacrynic acid and diamide both inhibited the caerulein (1 x 10(-9) mol/L)-induced Ca(2+) mobilization in pancreatic acinar cells. Neither ethacrynic acid nor diamide altered the CCK-receptor binding characteristics.


CONCLUSIONS
The present findings strongly suggest that glutathione plays a potential role in the secretory process in pancreatic acinar cells and in the secretory blockade observed in acute pancreatitis. A decrease of caerulein-induced Ca(2+) mobilization might participate in the effect of glutathione depletion on pancreatic exocrine secretory function.
Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan 430060, China.
Honggang
H
Yu
Hesheng
H
Luo
Geng
G
Tian
Jieping
J
Yu
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D002108:Ceruletide / Q000008:administration & dosage / Q000494:pharmacology; D002766:Cholecystokinin / Q000378:metabolism; D003958:Diamide / Q000494:pharmacology*; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D016877:Oxidants; D013438:Sulfhydryl Compounds; D003958:Diamide; D002108:Ceruletide; D002766:Cholecystokinin; D000681:Amylases; D005978:Glutathione; D004976:Ethacrynic Acid; D002118:Calcium