CHOLECYSTOKININ SUPPRESSES FOOD-INTAKE BY A NONENDOCRINE MECHANISM INRATS

A cholecystokinin monoclonal antibody (CCK MAb) was used to immunoneut ralize CCK to test the hypothesis that CCK produces satiety by an endo crine mechanism. We first characterized the effects of CCK MAb on panc reatic secretion. Conscious rats with jugular vein and bile-pancreatic duct cannulas received CCK MAb or control antibody intravenously 30 m in before a 2-h maximal dose of CCK-8 (200 pmol.kg(-1) h(-1) iv) or ac cess to food. CCK MAb caused dose-related inhibition of amylase secret ion. CCK MAb (2 mg/kg) completely blocked the response to CCK-8 and in hibited the response to food by 89%. In feeding experiments, rats with free access to food received CCK MAb or control antibodies (2 mg/kg i v) 2 h after lights off. CCK MAb had no effect on 1.5- or 3.5-h food i ntake. Another group of rats received CCK MAb (4 mg/kg iv) or a combin ed injection of type A and type B CCK receptor antagonists devazepide and L-365,260 (1 mg/kg each iv). CCK MAb had no effect on feeding, whe reas the receptor antagonists stimulated 1-, 2-, 3-, and 4-h intake by 62, 45, 43, and 29%. These results suggest that endogenous CCK stimul ates pancreatic enzyme secretion at least partially by an endocrine me chanism and produces satiety by a nonendocrine mechanism.