Potent cholecystokinin antagonist L 364718 stimulates food intake in rats.
The cholecystokinin (CCK) receptor antagonist L 364718 was used to examine the role of CCK in control of food intake. Effects of L 364718 (0.01-1 mg/kg ip) on the feeding response to a maximal inhibitory dose of cholecystokinin COOH-terminal octapeptide (CCK-8; 8 nmol/kg ip) and on food intake alone were determined in rats fed ad libitum during the dark cycle. CCK-8 suppressed feeding by 48%. L 364718 reversed this effect dose dependently; the minimal effective dose was 0.03 mg/kg, and complete reversal occurred at 0.1 and 0.3 mg/kg. L 364718 (0.03 mg/kg) caused a parallel, rightward shift in the dose-response curve to CCK-8 [1-128 nmol/kg, half-maximal effective dose (ED50) increased 16-fold] but did not alter the maximal response, consistent with competitive-like kinetics. L 364718 stimulated liquid and solid food intake dose-dependently by 11-35%. The minimal effective dose was 0.1 mg/kg; maximal stimulation occurred at 0.3 mg/kg. Duodenal infusion of bile-pancreatic juice did not alter the response. These results support an important role for CCK in control of food intake.
Reidelberger
R D
RD
Department of Physiology, Kansas University Medical Center, Kansas 66103.
O'Rourke
M F
MF
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology; D010189:Pancreatic Juice / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000494:pharmacology
D001570:Benzodiazepinones; D002766:Cholecystokinin; D000681:Amylases; D020109:Devazepide; D012844:Sincalide