Cholecystokinin antagonism by beta-carboline esters in the central nervous system in mice.
Two beta-carboline esters, methyl or ethyl beta-carboline-3-carboxylate, beta-CCM and beta-CCE, were found to antagonize the antinociceptive and satiety action of the sulfated octapeptide cholecystokinin (CCK8) which was administered intracisternally to mice. beta-CCM did not affect the antinociception induced by morphine. The two beta-carboline esters weakly inhibited the food intake in mice. However, when they were administered after CCK8 administration, they reversed the CCK8-induced satiety. Since the two beta-carboline esters have been previously shown to act as selective cholecystokinin (CCK) receptor antagonists in the isolated guinea-pig gallbladder muscle, they are suggested to antagonize the central action of CCK through acting on the CCK receptor in the central nervous system. The results obtained from the present paper also suggest that benzodiazepine receptor ligands seem in general to act as CCK receptor antagonists as well.
Itonaga
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Uruno
T
T
Kubota
K
K
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002243:Carbolines / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D004435:Eating / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000503:physiopathology; D013997:Time Factors
D002243:Carbolines; C024915:beta-carboline-3-carboxylic acid ethyl ester; D009020:Morphine; D002766:Cholecystokinin; C036150:beta-carboline-3-carboxylic acid methyl ester