Ethacrynic acid inhibits pancreatic exocrine secretion.
OBJECTIVE
The effect of ethacrynic acid on pancreatic exocrine secretion function and potential mechanisms of interference with the secretory process in pancreatic acinar cells were investigated.


METHODS
After incubation with ethacrynic acid for 30 min, 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
Ethacrynic acid decreased caerulein (0.1 nmol/L)-stimulated amylase release and the level of pancreatic acinar glutathione in a concentration-dependent fashion without a marked increase in cell damage. Ethacrynic acid also inhibited the caerulein (1 nmol/L)-induced Ca2+ mobilization in pancreatic acinar cells. But neither protein thiol nor CCK-receptor binding characteristics was altered by ethacrynic acid.


CONCLUSIONS
Ethacrynic acid inhibit pancreatic exocrine secretion by depletion of glutathione and down-regulation of caerulein-induced Ca2+ mobilization. Glutathione might play a potential role in the secretory process in pancreatic acinar cells and in the secretory blockade observed in acute pancreatitis.
Yu
H G
HG
Division of Gastroenterology, Hepatology, and Infectious Diseases, Department of Medicine, Heinrich-Heine-University of Duesseldorf, Duesseldorf, Germany. yuhonggang@yahoo.com
Klonowski-Stumpe
H
H
D000681:Amylases / Q000096:biosynthesis; D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002108:Ceruletide / Q000494:pharmacology; D003864:Depression, Chemical; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005978:Glutathione / Q000096:biosynthesis; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000378:metabolism*
D004791:Enzyme Inhibitors; D011949:Receptors, Cholecystokinin; D002108:Ceruletide; D000681:Amylases; D005978:Glutathione; D004976:Ethacrynic Acid; D002118:Calcium