A new CCK-A antagonist, KSG-504, administered intraduodenally, inhibits pancreatic secretion in rats.
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.
Moriyoshi
Y
Y
Department of Internal Medicine and Gastroenterology, Tokyo Women's Medical College, Japan.
Shiratori
K
K
Takeuchi
T
T
Watanabe
S
S
D000818:Animals; D002364:Caseins / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D004386:Duodenum; D008297:Male; D015394:Molecular Structure; D009281:Naphthalenes / Q000008:administration & dosage*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010421:Pentanoic Acids / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D002364:Caseins; D009281:Naphthalenes; D010421:Pentanoic Acids; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; C085253:KSG 504; D002766:Cholecystokinin