Submitted on August 15, 2005
Accepted on November 6, 2005
Effects of Pancreatic Duct Ligation on the Pancreatic Response to Bombesin
Taiichi Otani1*, Akira Matsukura2, Takeshi Takamoto2, Yasuji Seyama2, Yasuhito Shimizu3, Michiyo Shinomiya4, Hiroshi Usui5, Fred S. Gorelick6, and Masatoshi Makuuchi2
1 Department of Surgery, University of Tokyo, Tokyo, Japan; Department of Surgery, Ichijo-dori Hospital, Asahikawa, Japan
2 Department of Surgery, University of Tokyo, Tokyo, Japan
3 Department of Surgery, Tokyo Metropolitan Fuchu Hospital, Tokyo, Japan
4 Department of Applied Biological Science, Tokyo University of Science, Kashiwa, Japan
5 Department of Biochemistry and Molecular Biology, University of Tokyo, Tokyo, Japan
6 Departments of Medicine and Cell Biology, VAMC/Yale University, West Haven, CT, USA
* To whom correspondence should be addressed. E-mail: otanis{at}zc4.so-net.ne.jp.
To examine mechanisms that might be related to biliary pancreatitis, the effects of pancreatic duct ligation (PDL) with pancreatic stimulation have been examined in vivo. PDL alone caused no increase in pancreatic levels of trypsinogen activation peptide (TAP), trypsin, or chymotrypsin and did not initiate pancreatitis. Although bombesin caused zymogen activation within the pancreas, the increases were slight and it did not cause pancreatitis. However, the combination of PDL with bombesin resulted in prominent increases in pancreatic TAP, trypsin, chymotrypsin, and the appearance of TAP in acinar cells and caused pancreatitis. Disruption of the apical actin network in the acinar cell was observed when PDL was combined with bombesin, but not with PDL or bombesin alone. These studies suggest that when PDL is combined with pancreatic acinar cell stimulation it can promote zymogen activation, the retention of active enzymes in acinar cells, and the development of acute pancreatitis.
