The cholecystokinin receptor antagonist L364,718 increases food intake in the rat by attenuation of the action of endogenous cholecystokinin. |
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| Authors: | G. Hewson G. E. Leighton R. G. Hill J. Hughes |
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| Affiliation: | Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge. |
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| 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. |
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