Effects of selective cholecystokinin antagonists L364,718 and L365,260 on food intake in rats.
The selective type A and B cholecystokinin (CCK) receptor antagonists L364,718 and L365,260 were used to identify the receptor subtype that mediates the satiety effect of endogenous CCK. Male rats (n = 12-13/group), fed ground rat chow ad lib, received L364,718 (0, 1, 10, 100, or 1000 micrograms/kg IP) or L365,260 (0, 0.1, 1, 10, 100, 1000, or 10,000 micrograms/kg IP) 2 h after lights off, and food intake was measured 1.5, 3.5, and 5.5 h later. L364,718 significantly stimulated 1.5-h food intake by more than 40% at 10 micrograms/kg and higher doses; cumulative intake at 3.5 and 5.5 h remained elevated by about 20% at 1000 and 100 micrograms/kg of L364,718, respectively. In contrast, L365,260 had no significant stimulatory effect on feeding at any dose. The potency of L365,260 for antagonizing gastrin-stimulated gastric acid secretion was examined in unanesthetized rats. Male rats (n = 14), prepared with gastric and jugular vein cannulas, received doubling doses of gastrin (G-171) (0.16-5 nmol/kg/h IV), each dose for 30 min, and gastric juice was collected for each 30-min period. G-171 stimulated gastric acid output dose dependently; the minimal effective dose was 0.16 nmol/kg/h, while maximal output (5-fold above basal) occurred at 5 nmol/kg/h. L365,260 (0, 1, 10, 100, 1000, or 10,000 micrograms/kg IV), administered 30 min before continuous infusion of G-171 (1.25 or 5 nmol/kg/h), significantly inhibited acid output only at 10,000 micrograms/kg; cumulative 60-min output was decreased by 60%. These results suggest that CCK acts at CCK-A receptors to produce satiety during the dark period in ad lib-feeding rats.
Reidelberger
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Research Service, VA Medical Center, Omaha, NE 68105.
Varga
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Solomon
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D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology; D008297:Male; D010671:Phenylurea Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000145:classification / Q000502:physiology; D012527:Satiation / Q000187:drug effects / Q000502:physiology
D001570:Benzodiazepinones; D005755:Gastrins; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D020109:Devazepide