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• W2029227717 endingPage "1987" @default.
• W2029227717 startingPage "1980" @default.
• W2029227717 abstract "Abstract: Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate), a partial inverse agonist of brain benzodiazepine receptors, has been shown to antagonize some actions of ethanol. In addition to conventional benzodiazepine binding sites, Ro 15-4513 binds to a specific cerebellar protein, the binding of which has been shown to be insensitive to diazepam. The binding of [3H]Ro 15-4513 was studied in washed membranes of the cerebellum, hippocampus, and cerebral cortex of two rat lines developed for differences in their sensitivity to ethanol-induced motor impairment. Only minor differences were found in the estimated parameters (KD and Bmax) for the total specific binding between the rat lines. The main difference between the rat lines was, however, observed in the characteristics of the cerebellar binding, all of which was displaced by diazepam in most of the alcohol-sensitive [alcohol-nontolerant (ANT)] rats, in contrast to only 75% displacement in most of the alcohol-insensitive [alcohol-tolerant (AT)] ones. The following cerebellar results were obtained with the major subgroups of both lines, i.e., with the AT rats chosen for the presence of the diazepam-insensitive binding and with the ANT rats chosen for its absence. The KD for the total specific [3H]Ro 15-4513 binding in the ANT animals was about half of that in the AT animals. No line difference was found in the Bmax of the binding in these rats. Photolabeling with [3H]Ro 15-4513 showed that the diazepam-insensitive binding was in a protein with a molecular weight of 55,000. In the absence of diazepam, this band was labeled in both rat lines, but micromolar diazepam abolished the labeling more thoroughly in the ANT rats. There were only minor line differences in the potency of the inverse agonists ethyl-β-carboline-3-carboxylate, methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate, and FG 7142 (N-methyl-β-carboline-3-carboxamide) to displace the cerebellar [3H]Ro 15-4513 binding. This result suggests that the line difference has developed specifically in the affinity of the protein with a molecular weight of 55,000 to micromolar diazepam and possibly to other benzodiazepine agonists as well. Because the rat lines differ in their sensitivity to benzodiazepines in a similar way as to ethanol, the diazepam-insensitive binding sites of [3H]Ro 15-4513 might be involved in the mechanisms causing the impairment of motor performance after sedative drugs." @default.
• W2029227717 created "2016-06-24" @default.
• W2029227717 creator A5014779572 @default.
• W2029227717 creator A5085521126 @default.
• W2029227717 date "1990-06-01" @default.
• W2029227717 modified "2023-10-04" @default.
• W2029227717 title "Diazepam Sensitivity of the Binding of an Imidazobenzodiazepine, [³H]Ro 15-4513, in Cerebellar Membranes from Two Rat Lines Developed for High and Low Alcohol Sensitivity" @default.
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• W2029227717 doi "https://doi.org/10.1111/j.1471-4159.1990.tb04901.x" @default.
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