Amelioration of cholinergic-induced pancreatitis with a selective cholecystokinin receptor antagonist
A. J. Bilchik, K. A. Zucker, T. E. Adrian and I. M. Modlin
Department of Surgery, Yale University School of Medicine, New Haven, Conn.
Acute edematous pancreatitis follows excessive cholinergic stimulation in
patients exposed to anticholinesterase-containing insecticides. We describe
the role of cholecystokinin and the benefits of cholecystokinin receptor
blockade in this form of pancreatitis. A cholinergic mimetic (carbachol)
was administered to rats weighing 300 to 350 g and produced a form of
edematous pancreatitis that mimics that seen in humans. Animals received
carbachol intraperitoneally, either alone (250 micrograms/kg of body
weight) or with cholecystokinin-receptor antagonist devazepide (3 mg/kg of
body weight) and were killed 4 hours later. Carbachol administration
resulted in a 19% increase in pancreatic weight, a fourfold increase in
serum amylase levels, and a 14-fold increase in serum lipase levels. Plasma
cholecystokinin levels, however, were not altered. Devazepide administered
prior to cholinergic hyperstimulation blocked pancreatic weight increase
and reduced elevations in serum amylase levels twofold and lipase levels
fourfold. Although cholecystokinin levels are not elevated in this model of
pancreatitis, blockade of even low, background concentrations of this
regulatory peptide is beneficial.
