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• W2100055201 abstract "Rates of desensitization of a rapidly desensitizing 4-aminobutyrate (4-Abu) receptor (t1/2 = 33 ms at saturation) were measured in a previously characterized experimental system from rat cerebral cortex. Desensitization was measured at times between 100 ms and several s. Measurements with 300-ms or 1-s 82Br- influx assays after prior incubation of the membrane with 4-Abu covered the whole 4-Abu concentration range of response. Desensitization was not affected by the low Br- concentrations (< or = 1 mM) present. The presence of the tranquilizing drug chlordiazepoxide (Librium) in the prior incubation increased the desensitization rate at 4-Abu concentrations below saturation. This drug changed the dependence of desensitization rate on 4-Abu concentration from the sigmoid response, previously reported with 4-Abu alone, to a hyperbolic dependence. In the presence of chlordiazepoxide the measurements approximated linear Eadie-Hofstee and Lineweaver-Burk plots. This extended the range of response to lower 4-Abu concentrations, so that the relative increase of desensitization rate became larger with decreasing 4-Abu concentration and was about sixfold at 1 microM 4-Abu. The maximum rate, at saturation with 4-Abu was unchanged by chlordiazepoxide. This observation parallels the change in the mechanism of channel opening due to chlordiazepoxide previously reported. All the measurements could be fitted to a simple minimal kinetic model, in which the effect of chlordiazepoxide could be attributed to a change in the receptor with one bound 4-Abu molecule. This could be an increase in desensitization rate or a decrease in dissociation constant of the receptor with one bound 4-Abu molecule and no other change. The effects of the tranquilizer, chlordiazepoxide with this receptor are to extend the 4-Abu concentration range of response 10-fold, to lower 4-Abu concentrations, so that the major part of the response occurs between 0.3 microM and 1000 microM 4-Abu. In addition to the effect on channel opening, the receptor desensitization rate is affected in the same way." @default.
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• W2100055201 date "1995-03-01" @default.
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• W2100055201 title "Mechanism of Chlordiazepoxide Enhancement of 4-Aminobutyrate-Receptor Desensitization Investigated with 82Br- Radiotracer" @default.
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• W2100055201 doi "https://doi.org/10.1111/j.1432-1033.1995.0311n.x" @default.
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