Abstract
We studied the effect in anesthetized rats of a new cholecystokinin (CCK) receptor antagonist developed in Japan, KSG-504, administered intraduodenally, on pancreatic exocrine secretion stimulated by exogenous CCK and intraduodenal casein. Intraduodenal administration of KSG-504 in graded doses of 2.5-50 mg/kg/h produced dose-dependent inhibition of pancreatic juice volume and amylase output stimulated by intravenous infusion of CCK-8 in a dose of 0.06 micrograms/kg/h. The ID50 (half-maximal inhibition dose) of KSG-504 for CCK-8-stimulated amylase secretion was 3.4 mg/kg/h. Moreover, intraduodenal KSG-504 (5 and 25 mg/kg/h) dose dependently suppressed pancreatic juice volume, and amylase output increased with intraduodenal infusion of casein (400 mg/h). It is concluded that KSG-504 administered intraduodenally has a significant, potent inhibitory action on the exocrine pancreas stimulated by exogenous CCK and intraduodenal casein.
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