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Am J Physiol Gastrointest Liver Physiol 290: G633-G639, 2006. First published November 17, 2005; doi:10.1152/ajpgi.00377.2005
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HORMONES AND SIGNALING

Effects of pancreatic duct ligation on pancreatic response to bombesin

Taiichi Otani,1,3 Akira Matsukura,1 Takeshi Takamoto,1 Yasuji Seyama,1 Yasuhito Shimizu,4 Michiyo Shinomiya,5 Hiroshi Usui,2 Fred S. Gorelick,6 and Masatoshi Makuuchi1

Departments of 1Surgery and 2Biochemistry and Molecular Biology, University of Tokyo, Tokyo; 3Department of Surgery, Ichijo-dori Hospital, Asahikawa; 4Department of Surgery, Tokyo Metropolitan Fuchu Hospital, Tokyo; 5Department of Applied Biological Science, Tokyo University of Science, Kashiwa, Japan; and 6Departments of Medicine and Cell Biology, Veterans Affairs Medical Center, Yale University School of Medicine, West Haven, Connecticut

Submitted 15 August 2005 ; accepted in final form 6 November 2005

To examine mechanisms that might be related to biliary pancreatitis, we examined the effects of pancreatic duct ligation (PDL) with pancreatic stimulation 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.

pancreas; pancreatitis; trypsinogen activation peptide; trypsin



Address for reprint requests and other correspondence: T. Otani, Dept. of Surgery, Ichijo-dori Hospital, Toyo-oka 1-1, Asahikawa, Hokkaido 078-8231, Japan (e-mail: otanis{at}zc4.so-net.ne.jp)







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