title: The cholecystokinin receptor antagonist L364,718 increases food intake in the rat by attenuation of the action of endogenous cholecystokinin.
abstract: 1. To determine the role of endogenous cholecystokinin (CCK) in the regulation of food intake, the effects of the potent CCK receptor antagonist L364,718 were investigated on the intake of a palatable diet in non-deprived rats. The effect of a single dose of proglumide was also investigated for comparative purposes. In addition, the ability of L364,718 to antagonize the reduction in food intake produced by exogenous cholecystokinin-octapeptide (CCK8) or bombesin in food-deprived rats was determined. 2. L364,718 (10-100 micrograms kg-1, i.p.) increased the intake of palatable diet during the 30 min test period. Proglumide (300 mg kg-1, i.p.) also increased the intake of palatable diet. Conversely, CCK8 (0.5-5 micrograms kg-1, i.p.) produced a reduction in the intake of the diet. 3. In fasted rats, L364,718 (100 micrograms kg-1, i.p.) antagonized the reduction in food intake produced by CCK8 (10 micrograms kg-1, i.p.) but not that produced by bombesin (50 micrograms kg-1, i.p.). L364,718 did not increase food intake in these animals when measured over a 6 h period. 4. It is concluded that L364,718 is a potent, selective antagonist of the effects of CCK8 on food intake. The observation that L364,718 and proglumide increase the intake of a palatable diet provides some evidence that endogenous CCK is involved in the control of food intake in this model.
authors.affiliation: Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge.
authors.forename: G
authors.initials: G
authors.lastname: Hewson
authors.forename: G E
authors.initials: GE
authors.lastname: Leighton
authors.forename: R G
authors.initials: RG
authors.lastname: Hill
authors.forename: J
authors.initials: J
authors.lastname: Hughes
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D001839:Bombesin / Q000494:pharmacology; D002766:Cholecystokinin / Q000378:metabolism* / Q000494:pharmacology; D020109:Devazepide; D004032:Diet; D004435:Eating / Q000187:drug effects*; D005215:Fasting; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D020109:Devazepide; D001839:Bombesin