Effect of CCK antagonist L 364718 on meal-induced pancreatic secretion in rats.
The specific cholecystokinin (CCK)-receptor antagonist L 364718 was used to examine the role of CCK in meal-induced pancreatic secretion. Unanesthetized rats with gastric, jugular vein, bilepancreatic, and duodenal cannulas were used; bile-pancreatic juice was recirculated. Basal amylase secretion (30% of maximal) was not inhibited by L 364718 doses of 0.5 or 2 mg/kg intravenously. L 364718 (0.02 to 2 mg/kg) caused dose-related inhibition of the maximal amylase response to CCK-8 (200 pmol.kg-1.h-1), with greater than 80% inhibition at doses greater than or equal to 0.5 mg/kg. L 364718 (0.5 mg/kg) shifted the dose-response curve to CCK-8 (25-3,200 pmol.kg-1.h-1) to the right (ED50 increased 10-fold) but did not alter maximal amylase output consistent with competitive inhibition of CCK in vivo. Ingestion of liquid food significantly increased amylase output threefold above basal. L 364718 (0.5 mg/kg) completely blocked this response. These results suggest that although CCK does not regulate basal pancreatic enzyme secretion, it is the primary mediator of pancreatic enzyme secretion in response to a liquid meal.
Department of Physiology, University of Missouri Medical School, Columbia 65211.
M F
MF
O'Rourke
R D
RD
Reidelberger
T E
TE
Solomon
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D004435:Eating; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001570:Benzodiazepinones; D002766:Cholecystokinin; D000681:Amylases; D020109:Devazepide; D012844:Sincalide