Effects of short-term administration of the CCK receptor antagonist, KSG-504, on regeneration of pancreatic acinar cells in acute pancreatitis in rats.
Cholecystokinin (CCK) receptor antagonists have been reported on have an inhibitory effect on acute experimental pancreatitis, but their long-term administration is also reported to block pancreatic regeneration. We examined whether the short-term administration of KSG-504 (KSG), a synthetic CCK-A receptor antagonist, inhibited the regeneration of pancreatic acinar cells after ethionine-induced acute pancreatitis in rats. KSG (50 mg/kg), given 12 times by subcutaneous injection at 6-h intervals, prevented the reduction of protein, amylase, and trypsinogen levels, and the DNA content of the pancreas and facilitated the recovery of these values. Ornithine decarboxylase activity in pancreatic tissue and a 5-bromo-2'-deoxyuridine labeling study indicated that DNA synthesis was accelerated in rats treated with KSG. These findings suggest that the short-term administration of KSG inhibits the development of ethionine-induced acute pancreatitis and facilitates the regeneration of acinar cells.
Okumura
Y
Y
Department of Internal Medicine, Shiga University of Medical Science, Japan.
Inoue
H
H
Fujiyama
Y
Y
Bamba
T
T
D000208:Acute Disease; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D004247:DNA / Q000032:analysis; D005001:Ethionine; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage* / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism / Q000502:physiology*; D010195:Pancreatitis / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D010421:Pentanoic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D012038:Regeneration / Q000187:drug effects*
D009281:Naphthalenes; D010421:Pentanoic Acids; D011949:Receptors, Cholecystokinin; C085253:KSG 504; D004247:DNA; D009955:Ornithine Decarboxylase; D001973:Bromodeoxyuridine; D005001:Ethionine