Cholecystokinin acts as an essential factor in the exacerbation of pancreatic bile duct ligation-induced rat pancreatitis model under non-fasting condition
G. Yoshinaga et al., Cholecystokinin acts as an essential factor in the exacerbation of pancreatic bile duct ligation-induced rat pancreatitis model under non-fasting condition, JPN J PHARM, 84(1), 2000, pp. 44-50
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.