Autoradiographic demonstration of the antagonism of anthramycin and diazepam against cholecystokinin in the mouse brain using the [14C]-2-deoxyglucose method.
Effects of diazepam (DZP), a synthetic benzodiazepine drug, and anthramycin (ATM), a benzodiazepine antitumor antibiotic produced by a certain species of streptomyces, on the uptake of 2-deoxy-D-[14C]-glucose (2-DG) in mouse brain neurons with or without cholecystokinin were examined. 2-DG uptake in neurons was evaluated by using an autoradiographic technique. The sulfated octapeptide CCK (CCK8) was injected intracisternally; DZP and ATM, intraperitoneally; and 2-DG, intravenously to mice. Autoradiograms prepared from the slices of the brain were converted to false color images. CCK8 (1 microgram/mouse) markedly stimulated the 2-DG uptake in neurons in the various regions of the brain, but the stimulative effects of CCK8 was almost completely suppressed after an intraperitoneal administration of 1.0 mg/kg of DZP or 0.5 mg/kg of ATM. Since it has been previously shown that these doses of DZP and ATM almost completely reversed the antinociception produced by 1 microgram/mouse of CCK8, the present results on the 2-DG uptake in the mouse brain are considered to further support the antagonism between CCK8 and DZP or ATM in the central nervous system.
Sugaya
K
K
Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Kubota
K
K
D000818:Animals; D000876:Anthramycin / Q000494:pharmacology*; D001345:Autoradiography; D001570:Benzodiazepinones / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D003847:Deoxyglucose / Q000493:pharmacokinetics; D003975:Diazepam / Q000494:pharmacology*; D008297:Male; D051379:Mice
D001570:Benzodiazepinones; D000876:Anthramycin; D002766:Cholecystokinin; D003847:Deoxyglucose; D003975:Diazepam