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 micrograms/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 microgram/kg) not active by the IV route, significantly reduced (p less than 0.01) by 67.5% the feeding-induced colonic hyperactivity. In contrast, L365,260 (1-10 micrograms/kg ICV) injected was inactive. Increase in colonic motility produced by intravenous CCK8 infusion (1 microgram/kg/h) was suppressed by previous ICV and IV administration of L364,718 at doses of 1 and 10 micrograms/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 CCKA receptors.
Department of Pharmacologie INRA, Toulouse, France.
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D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D020109:Devazepide; D004285:Dogs; D004435:Eating / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000145:classification / Q000502:physiology*
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D020109:Devazepide