Abdominal vagal mediation of the satiety effects of exogenous and endogenous cholecystokinin in rats

The hypothesis that peripherally administered cholecystokinin C-terminal octapeptide (CCK-8) and endogenous CCK act by the same abdominal vagal mechanism to produce satiety was tested by injecting rats with CCK-8 or the type A CCK receptor antagonist MK-329 after they had received bilateral subdiaphragmatic vagotomies. CCK-8 (8 nmol/kg ip) inhibited 1-h food intake by 60%; vagotomy and MK-329 (0.5 mg/kg sc) each completely blocked this effect. In contrast, vagotomy did not alter the stimulatory effect of MK-329 (0.5 mg/kg sc) on feeding; 3-h cumulative intake in control and vagotomized animals was increased by 25 and 34%, respectively. These results suggest that satiety is mediated in part by an endogenous CCK action that is independent of abdominal vagal innervation.