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 r...

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Bibliographic Details
Published in:Journal of gastroenterology 1995-08, Vol.30 (4), p.493-499
Main Authors: Okumura, Y, Inoue, H, Fujiyama, Y, Bamba, T
Format: Article
Language:English
Subjects:
Acute Disease
Animals
Bromodeoxyuridine - metabolism
DNA - analysis
Ethionine
Male
Naphthalenes - administration & dosage
Naphthalenes - pharmacology
Ornithine Decarboxylase - metabolism
Pancreas - metabolism
Pancreas - physiology
Pancreatitis - chemically induced
Pancreatitis - physiopathology
Pancreatitis - prevention & control
Pentanoic Acids - administration & dosage
Pentanoic Acids - pharmacology
Rats
Rats, Wistar
Receptors, Cholecystokinin - antagonists & inhibitors
Regeneration - drug effects
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Summary: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.
ISSN:0944-1174
1435-5922
DOI:10.1007/BF02347566