Effect of KSG-504, a new synthetic cholecystokinin receptor antagonist on ethionine-induced acute pancreatitis in rats

Abstract

KSG-504, a new synthetic cholecystokinin (CCK) receptor antagonist derived from proglumide, has superior selectivity and affinity to CCK-A receptors. We have investigated the effect of KSG-504 on ethionine-induced acute pancreatitis in rats and the influence of endogenous CCK on evolution of pancreatitis and regeneration of pancreatic acinar cells. Reduction of pancreatic proteins and digestive enzyme contents was dose-dependently prevented by subcutaneous administration of KSG-504. The inhibition of evolution of pancreatitis was demonstrated histologically in KSG-504 treated rats. The effect of KSG-504 on pancreatic regeneration was evaluated by bromodeoxyuridine labeling index (B.L.I.) of acinar cells. There was no significant difference of B.L.I. between KSG-504 treated and non-treated rats. These results suggest that KSG-504 has a beneficial effect on ethionine-induced acute pancreatitis by blockade of endogenous CCK.