CENTRAL AND PERIPHERAL EFFECTS OF CCK RECEPTOR ANTAGONISTS ON SATIETYIN 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) rece ptor antagonists in esophageal-fistula dogs. Suppression of feeding wa s induced by either balloon gastric distension or small bowel nutrient infusion and was measured as the volume sham fed. Intracerebroventric ular L-365,260 abolished satiety behavior from gastric distension (vol ume 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 satie ty 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 dist ension. 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 physiolog ical mediator of satiety behavior from gastric distension but not smal l bowel nutrients and, in the periphery, CCK is a physiological mediat or of satiety behavior from small bowel nutrients but not gastric dist ension.