Pancreatic edema and intrapancreatic activation of trypsinogen
during secretagogue-induced pancreatitis in rats preceeds glutathione
depletion.
Grady, T., A. Saluja, A. Kaiser, D. McNally, and M. Steer.
Department of Surgery, Beth Israel Hospital and Harvard Medical
School, Harvard Digestive Diseases Center, Boston, MA 02215 and
Abbott Laboratories, Abbott Park, IL
APStracts 2:0247G, 1995.
Acute pancreatitis is characterized by hyperamylasemia, pancreatic
edema, and the presence of activated digestive enzymes within the
pancreas. The secretagogue-induced model of acute pancreatitis is
also characterized by pancreatic acinar cell vacuolization,
subcellular redistribution of lysosomal hydrolases, and a fall in
pancreatic glutathione levels. We have performed time-dependence
studies to determine the sequence with which these phenomena appear
and to establish their cause-effect relationship. Evidence of
lysosomal enzyme redistribution and trypsinogen activation within the
pancreas could be detected within 10-15 min of the onset of
supramaximal secretagogue stimulation while hyperamylasemia (30 min),
pancreatic edema (60 min), and acinar cell vacuolization (60 min)
occurred at later times. Pancreatic glutathione levels were either
unchanged ( 15 and 30 min) or elevated (60 min) during the early
times of supramaximal stimulation and were only noted to be decreased
at a later time. These results support the conclusion that
intrapancreatic digestive enzyme activation, possibly occurring by a
mechanism which involves lysosomal hydrolase redistribution, is an
early and likely a critical event in the evolution of secretagogue
-induced pancreatitis but that glutathione depletion is neither an
early event nor an event which is critical to the evolution of this
model of pancreatitis.
Received 28 June 1995; accepted in final form 25 October 1995.
APS Manuscript Number G276-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95