Effect of ethanol on cholecystokinin-stimulated zymogen conversion
in pancreatic acinar cells.
Katz, Mark, Robert Carangelo, Laurence J. Milleri, Fred Gorelick.
The Departments of Medicine, Cell BiologyN, and Surgery, West Haven
VA Medical Center and Yale School of Medicine, New Haven, CT and the
Mayo Clinic Foundationi, Rochester, MN
APStracts 2:0164G, 1995.
Exocrine pancreatic zymogens are proteolytically processed to active
forms after they are secreted into the small intestine. However,
intracellular conversion of zymogens to active forms can be
stimulated by treating pancreatic acinar cells with high doses [10 M]
of cholecystokinin or [100 mM] carbamylcholine. The high doses of
cholecystokinin are unlikely to be achieved physiologically. The
ability of ethanol to sensitize the acinar cell to zymogen conversion
induced by cholecystokinin or carbamylcholine was examined. Ethanol
[10-200 mM] had no effect alone or when combined with
carbamylcholine. However, ethanol [25 mM] added with low dose
cholecystokinin [0.1 nM] generated zymogen conversion that was: a)
higher than cholecystokinin alone, and b) equivalent to that
generated by high dose cholecystokinin [10 M]. The ability of ethanol
to sensitize the acinar cell was dependent on the ethanol dose and
its duration of treatment. The cholecystokinin receptor antagonist,
L-364,718, blocked the conversion stimulated by the addition of
ethanol with cholecystokinin. This effect of ethanol did not change
in the affinity or number of cholecystokinin receptors, suggesting an
effect more distal in the stimulus-activation cascade. These findings
demonstrate that ethanol selectively sensitizes the pancreatic acinar
cell to cholecystokinin-stimulated zymogen proteolysis.
Received 22 February 1995; accepted in final form 26 July 1995.
APS Manuscript Number G77-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.