Central and peripheral effects of CCK receptor antagonists on satiety in dogs

The role of cholecystokinin (CCK) as a central and peripheral satiety factor was studied using the CCK-B (L-365,260) and CCK-A (MK-329) receptor antagonists in esophageal-fistula dogs. Suppression of feeding was induced by either balloon gastric distension or small bowel nutrient infusion and was measured as the volume sham fed. Intracerebroventricular L-365,260 abolished satiety behavior from gastric distension (volume sham fed 2,667 +/- 211 ml vs. vehicle alone 1,217 +/- 446 ml, P < 0.05) but not small bowel infusion. Intravenous MK-329 abolished satiety behavior from small bowel infusion (volume sham fed 1,900 +/- 521 ml vs. vehicle alone 210 +/- 198 ml, P < 0.05) but not from gastric distension. The volume sham fed after intracerebroventricular MK-329 with balloon gastric distension or small bowel infusion did not differ from control. These results suggest that, in the brain, CCK is a physiological mediator of satiety behavior from gastric distension but not small bowel nutrients and, in the periphery, CCK is a physiological mediator of satiety behavior from small bowel nutrients but not gastric distension.