Alcohols enhance caerulein-induced zymogen activation in pancreatic acinar cells.
Activation of zymogens within the pancreatic acinar cell is an early feature of acute pancreatitis. Supraphysiological concentrations of cholecystokinin (CCK) cause zymogen activation and pancreatitis. The effects of the CCK analog, caerulein, and alcohol on trypsin and chymotrypsin activation in isolated pancreatic acini were examined. Caerulein increased markers of zymogen activation in a time- and concentration-dependent manner. Notably, trypsin activity reached a peak value within 30 min, then diminished with time, whereas chymotrypsin activity increased with time. Ethanol (35 mM) sensitized the acinar cells to the effects of caerulein (10(-10) to 10(-7) M) on zymogen activation but had no effect alone. The effects of ethanol were concentration dependent. Alcohols with a chain length of >or=2 also sensitized the acinar cell to caerulein; the most potent was butanol. Branched alcohols (2-propanol and 2-butanol) were less potent than aliphatic alcohols (1-propanol and 1-butanol). The structure of an alcohol is related to its ability to sensitize acinar cells to the effects of caerulein on zymogen activation.
Lu
Zhao
Z
Department of Internal Medicine, Section of Digestive Diseases, and Cell Biology, Veterans Administration Connecticut Healthcare, West Haven 06516, USA.
Karne
Suresh
S
Kolodecik
Thomas
T
Gorelick
Fred S
FS
D019840:2-Propanol / Q000494:pharmacology; D000208:Acute Disease; D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D000440:Butanols / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology*; D002918:Chymotrypsin / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology; D010195:Pancreatitis / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014357:Trypsin / Q000378:metabolism
D000438:Alcohols; D000440:Butanols; D004792:Enzyme Precursors; C043958:2-butanol; D000431:Ethanol; D002108:Ceruletide; D002918:Chymotrypsin; D014357:Trypsin; D019840:2-Propanol