EFFECT OF IRSOGLADINE ON GAP-JUNCTIONS IN CERULEIN-INDUCED ACUTE-PANCREATITIS IN RATS

Citation
T. Ito et al., EFFECT OF IRSOGLADINE ON GAP-JUNCTIONS IN CERULEIN-INDUCED ACUTE-PANCREATITIS IN RATS, Pancreas, 15(3), 1997, pp. 297-303
Citations number
45
Journal title
ISSN journal
08853177
Volume
15
Issue
3
Year of publication
1997
Pages
297 - 303
Database
ISI
SICI code
0885-3177(1997)15:3<297:EOIOGI>2.0.ZU;2-#
Abstract
The capacity for intercellular communication (IC) via gap junctions is found in normal pancreatic acinar cells. The major role of IC is cons idered to be the maintenance of tissue homeostasis and the regulation of signal transmissions. Up to now, the participation of IC via gap ju nctions in acute pancreatitis has not been reported. We investigated t he role of IC in cerulein (Cn)-induced acute pancreatitis in rats usin g irsogladine, an enhancer of IC via gap junction. Acute edematous pan creatitis was induced in rats by two intraperitoneal injections of 40 mu g/kg Cn. Rats received various doses (25, 50, or 100 mg/kg body wei ght) of irsogladine orally, 15 and 2 h before the first Cn injection. The normal control group received only vehicle. The severity of pancre atitis was evaluated enzymatically and histologically 5 h after the fi rst Cn injection. In Cn-induced acute pancreatitis, irsogladine signif icantly lowered the serum amylase level, the pancreatic wet weight, an d the pancreatic amylase and DNA contents, in a dose-dependent manner. Particularly, the amylase content improved to the level of the normal controls. Histologically, the severity of pancreatitis was reduced si gnificantly by treatment with irsogladine and no discernible vacuoliza tion was seen in the group with 100 mg/kg irsogladine treatment. By im munofluorostaining pancreata with anti-connexin 32 (Cx32; a gap juncti on protein) antibody, we found that pancreatic acini were diffusely po sitive for Cx32 in the control group, but the number of Cx32-positive grains decreased markedly, to 19%, in the pancreatitis group. With 100 mg/kg irsogladine treatment, the number of Cx32 grains recovered to 7 0% of the normal control value. These findings indicate that IC via ga p junction is disturbed in Cn-induced pancreatitis, which may result i n the breakdown of tissue homeostasis and the progression of acute pan creatitis.