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.