Cholecystokinin acts as an essential factor in the exacerbation of pancreatic bile duct ligation-induced rat pancreatitis model under non-fasting condition

We examined the influence of 2 gut hormones involved in the enhancement of pancreatic exocrine secretion, secretin and cholecystokinin (CCK), in the e xacerbation of pancreatitis. We also examined the role of the vagal system, which was considered to be a transmission route for these hormones. Our mo del of pancreatitis in the rat was prepared by pancreatic bile duct ligatio n (PBDL), which simultaneously ligated the pancreatic duct and the common b ile duct. Serum amylase activity and histopathological changes in the pancr eas were used as indices of pancreatitis. We also measured the volume of pa ncreatic juice, as well as the amylase activity and protein level of the pa ncreatic juice, as indices of increased pancreatic exocrine secretion. Two gut hormones were given 6 times at 1-h intervals. Administration of secreti n (1 - 3 mu g/kg, s.c.) did not influence serum amylase activity in rats wi th PBDL-induced pancreatitis. However, food stimulation and administration of CCK-8 (1 mu g/kg, s.c.) increased serum amylase activity and promoted va cuolation of the pancreatic acinar cells in rats with PBDL-induced pancreat itis. Administration of atropine (3 mg/kg, s.c.) or a CCK1-receptor antagon ist, Z-203 (0.1 mg/kg, i.v.), inhibited food-stimulated or CCK-8-induced (1 mu g/kg, s.c.) enhancement of pancreatic exocrine secretion and exacerbati on after the development of PBDL-induced pancreatitis. These results sugges t that not secretin, which regulates the volume of pancreatic juice, but CC K, which regulates the secretion of pancreatic enzymes via the vagal system , plays an essential role in food-stimulated exacerbation after the develop ment of pancreatitis.