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Departments of Internal Medicine, Section of Digestive Diseases, and Cell Biology, Veterans Administration Connecticut Healthcare, West Haven and Yale University School of Medicine, New Haven, Connecticut 06516
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
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.
trypsinogen activation peptide; trypsin; chymotrypsin; ethanol; pancreatitis
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