Role of hypothalamic cholecystokinin octapeptide in the colonic motor response to a meal in rats.
The effects of hypothalamic microinfusions of cholecystokinin octapeptide and its antagonist L364,718 on cecocolonic myoelectrical activity were evaluated by electromyography in fasted and fed rats. The rats were chronically fitted with electrodes implanted on the cecum and proximal colon and cannulas placed bilaterally in either the ventromedial or lateral hypothalamus. In fasted rats, microinfusion of cholecystokinin octapeptide (10 ng/kg) into the ventromedial hypothalamus increased the spike-burst frequency of the cecum and the colon by 45.6% and 43.7%, respectively, during the 30-minute period after treatment. The injection of cholecystokinin octapeptide (10 ng/kg) into the lateral hypothalamus had no effect on either cecal or colonic motility. Feeding increased the frequency of cecal and colonic spike bursts by 52.1% and 50.1% for 30 minutes postprandially. When infused bilaterally into the ventromedial hypothalamus 10 minutes before feeding, L364,718 (1 or 5 micrograms/kg) abolished the increase of the frequency of cecal and colonic contractions induced by the meal. Infused into the lateral hypothalamus at similar dosages, L364,718 had no effect on the postprandial enhancement of cecocolonic motility. Increase of cecocolonic spike-burst frequency induced by feeding or by cholecystokinin octapeptide injected into the ventromedial hypothalamus was abolished by previous intracerebroventricular but not intraperitoneal administration of atropine (1 microgram) and 4-diphenylacetoxy-N-methylpiperidine (1 microgram), a selective muscarinic M2-receptor antagonist. In contrast, pirenzepine (1 microgram, intracerebroventricularly) did not significantly reduce the meal- or cholecystokin octapeptide-induced increase in cecal and colonic motility. These results suggest that, in rats, (a) cholecystokinin octapeptide is involved in the generation of the cecocolonic motor response to a meal and these effects are mediated through cholecystokinin octapeptide receptors located in the ventromedial hypothalamic nuclei, and (b) these postprandial colonic motor changes involve central cholinergic activation through muscarinic M2 receptors.
Liberge
M
M
Department of Pharmacology, Institut National de la Recherche Agronomique, Toulouse, France.
Arruebo
M P
MP
Bueno
L
L
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D003106:Colon / Q000502:physiology*; D020109:Devazepide; D004576:Electromyography; D005502:Food; D005769:Gastrointestinal Motility / Q000502:physiology*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000502:physiology; D012844:Sincalide / Q000008:administration & dosage / Q000494:pharmacology*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology
D001570:Benzodiazepinones; D010276:Parasympatholytics; D010880:Piperidines; D011949:Receptors, Cholecystokinin; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide