Jpn. J. Pharmacol. 84 (1), 44-50 (2000)

Cholecystokinin Acts as an Essential Factor in the Exacerbation of Pancreatic Bile Duct Ligation-Induced Rat Pancreatitis Model Under Non-fasting Condition

Koji Yoshinaga, Masataka Washizuka and Yoshihide Segawa*

Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., 2512-1 Oshikiri, Kohnan-machi, Ohsato-gun, Saitama 360-0111, Japan
* To whom correspondence should be addressed.

Abstract: We examined the influence of 2 gut hormones involved in the enhancement of pancreatic exocrine secretion, secretin and cholecystokinin (CCK), in the exacerbation of pancreatitis. We also examined the role of the vagal system, which was considered to be a transmission route for these hormones. Our model of pancreatitis in the rat was prepared by pancreatic bile duct ligation (PBDL), which simultaneously ligated the pancreatic duct and the common bile duct. Serum amylase activity and histopathological changes in the pancreas were used as indices of pancreatitis. We also measured the volume of pancreatic juice, as well as the amylase activity and protein level of the pancreatic juice, as indices of increased pancreatic exocrine secretion. Two gut hormones were given 6times at 1-h intervals. Administration of secretin (1-3mg/kg,s.c.) did not influence serum amylase activity in rats with PBDL-induced pancreatitis. However, food stimulation and administration of CCK-8 (1mg/kg,s.c.) increased serum amylase activity and promoted vacuolation of the pancreatic acinar cells in rats with PBDL-induced pancreatitis. Administration of atropine (3mg/kg,s.c.) or a CCK1-receptor antagonist, Z-203 (0.1mg/kg,i.v.), inhibited food-stimulated or CCK-8-induced (1mg/kg,s.c.) enhancement of pancreatic exocrine secretion and exacerbation after the development of PBDL-induced pancreatitis. These results suggest that not secretin, which regulates the volume of pancreatic juice, but CCK, which regulates the secretion of pancreatic enzymes via the vagal system, plays an essential role in food-stimulated exacerbation after the development of pancreatitis.

Keywords: Pancreatic bile duct ligation (PBDL), Pancreatitis, Cholecystokinin

Copyright The Japanese Pharmacological Society 2000

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