Glutathione might exert an important function in caerulein-stimulated amylase release in isolated rat pancreatic acini.
OBJECTIVE
The effect of different modes of thiol depletion on pancreatic exocrine secretory function and potential mechanisms of interference with the secretory process in pancreatic acinar cells were investigated.


METHODS
After incubation with three thiol-modulating agents (L-buthionine sulfoximine, ethacrynic acid, and diamide) for 30 minutes, caerulein-stimulated amylase release and cholecystokinin (CCK) receptor binding characteristics were assessed in isolated rat pancreatic acini. The level of thiol groups (glutathione and protein thiols) and cytosolic-free calcium were measured in pancreatic acinar cells.


RESULTS
All three thiol-modulating agents decreased caerulein (10(-10)M)-stimulated amylase release and the level of pancreatic acinar glutathione in a dose-dependent fashion without a marked increase in cell damage. Diamide also diminished the level of protein thiols. Ethacrynic acid and diamide, but not L-buthionine sulfoximine, inhibited the caerulein (10(-9)M)-induced Ca(2+) mobilization in pancreatic acinar cells. None of the three thiol-modulating agents altered the CCK receptor binding characteristics.


CONCLUSIONS
The present findings strongly suggest an important role of glutathione in the secretory process in pancreatic acinar cells and in the secretory blockade observed in acute pancreatitis. A decrease in caerulein-induced Ca(2+) mobilization might participate in the inhibition of amylase release by some oxidative agents, but it is not the prominent cause in general.
Yu
Honggang
H
Division of Gastroenterology, Hepatology, and Infectious Diseases, Department of Medicine, Heinrich-Heine-University of Duesseldorf, Duesseldorf, Germany.
Klonowski-Stumpe
Hanne
H
Lüthen
Reinhard
R
D000681:Amylases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002108:Ceruletide; D003958:Diamide / Q000494:pharmacology; D004976:Ethacrynic Acid / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D013439:Sulfhydryl Reagents; D003958:Diamide; D019328:Buthionine Sulfoximine; D002108:Ceruletide; D000681:Amylases; D005978:Glutathione; D004976:Ethacrynic Acid; D002118:Calcium