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Am J Physiol Regul Integr Comp Physiol 257: R1512-R1518, 1989;
0363-6119/89 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 257, Issue 6 1512-R1518, Copyright © 1989 by American Physiological Society


ARTICLES

Potent cholecystokinin antagonist L 364718 stimulates food intake in rats

R. D. Reidelberger and M. F. O'Rourke
Department of Physiology, Kansas University Medical Center, Kansas 66103.

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.


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