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 6ﾊtimes at 1-h intervals. Administration
of secretin (1-3ﾊmg/kg,ﾊs.c.) did not influence
serum amylase activity in rats with PBDL-induced pancreatitis. However,
food stimulation and administration of CCK-8 (1ﾊmg/kg,ﾊs.c.)
increased serum amylase activity and promoted vacuolation of the pancreatic
acinar cells in rats with PBDL-induced pancreatitis. Administration of atropine
(3ﾊmg/kg,ﾊs.c.) or a CCK1-receptor antagonist, Z-203 (0.1ﾊmg/kg,ﾊi.v.),
inhibited food-stimulated or CCK-8-induced (1ﾊmg/kg,ﾊ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ｩ The Japanese Pharmacological Society 2000
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