BRAIN CCKA RECEPTORS MEDIATE THE COLONIC MOTOR RESPONSE TO FEEDING IN DOGS

The influence of central vs. peripheral administration of specific type A and type B CCK receptor antagonists (L364,718 and L365,260, respectively) on colonic motor hyperactivity induced by feeding and CCK8 was investigated in dogs with strain-gauge transducers implanted on the proximal and transverse colon. Intravenous injection of L364,718 (5 and 10-mu-g/kg) reduced by 26.2% and 80.1%, respectively, the 0-4-h postprandial increase in colonic motor index; at similar doses L365,260 had no effect. Intracerebroventricular administration of L364,718, at a dose (1-mu-g/kg) not active by the IV route, significantly reduced (p < 0.01) by 67.5% the feeding-induced colonic hyperactivity. In contrast, L365,260 (1-10-mu-g/kg ICV) injected was inactive. Increase in colonic motility produced by intravenous CCK8 infusion (1-mu-g/kg/h) was suppressed by previous ICV and IV administration of L364,718 at doses of 1 and 10-mu-g/kg, respectively, while L365,260 was inactive at similar doses. It is concluded that CCK8 released after a meal is responsible for the postprandial increase in colonic motility and that these effects may be mediated through activation of central CCK(A) receptors.