Effect of Irsogladine on gap junctions in cerulein-induced acute pancreatitis in rats.
The capacity for intercellular communication (IC) via gap junctions is found in normal pancreatic acinar cells. The major role of IC is considered to be the maintenance of tissue homeostasis and the regulation of signal transmissions. Up to now, the participation of IC via gap junctions in acute pancreatitis has not been reported. We investigated the role of IC in cerulein (Cn)-induced acute pancreatitis in rats using irsogladine, an enhancer of IC via gap junction. Acute edematous pancreatitis was induced in rats by two intraperitoneal injections of 40 micrograms/kg Cn. Rats received various doses (25, 50, or 100 mg/kg body weight) of irsogladine orally, 15 and 2 h before the first Cn injection. The normal control group received only vehicle. The severity of pancreatitis was evaluated enzymatically and histologically 5 h after the first Cn injection. In Cn-induced acute pancreatitis, irsogladine significantly lowered the serum amylase level, the pancreatic wet weight, and 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 significantly by treatment with irsogladine and no discernible vacuolization was seen in the group with 100 mg/kg irsogladine treatment. By immunofluorostaining pancreata with anti-connexin 32 (Cx32; a gap junction protein) antibody, we found that pancreatic acini were diffusely positive 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 70% of the normal control value. These findings indicate that IC via gap junction is disturbed in Cn-induced pancreatitis, which may result in the breakdown of tissue homeostasis and the progression of acute pancreatitis.
Ito
T
T
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Ogoshi
K
K
Nakano
I
I
Ueda
F
F
Sakai
H
H
Kinjo
M
M
Nawata
H
H
D000208:Acute Disease; D000681:Amylases / Q000097:blood / Q000378:metabolism; D000818:Animals; D002108:Ceruletide; D017630:Connexins / Q000032:analysis; D004247:DNA / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000187:drug effects*; D008297:Male; D009929:Organ Size; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000494:pharmacology* / Q000627:therapeutic use; D000097002:Gap Junction beta-1 Protein
D000681:Amylases; D002108:Ceruletide; D017630:Connexins; D004247:DNA; D014227:Triazines; D000097002:Gap Junction beta-1 Protein; C041836:irsogladine