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Seifert J, Casida JE: Regulation of [35S] t-butylbicyclophosphorothionate binding sites in rat brain by GABA, pyrethroid and barbiturate. Eur J Pharmacol. 1985 Sep 24;115(2-3):191-8.
GABA regulates the binding of [35S] t-butylbicyclophosphorothionate ([35S] TBPS) within the GABA receptor-ionophore complex by decreasing the rate of radioligand association and increasing the rate of dissociation but in different ways for the EDTA/water-dialyzed rat brain membranes and a solubilized preparation obtained on treatment with the zwitterionic detergent CHAPS. In the membranes, GABA at 0.3-1 microM is a non-competitive inhibitor of [35S] TBPS binding, affecting the density of binding sites but not the affinity of the receptor, while at 5 microM both the apparent density and affinity are significantly decreased. On treatment with CHAPS the solubilized preparation and the corresponding pellet fraction become less sensitive to GABA which even at 5 microM acts only as a non-competitive inhibitor. CHAPS solubilization decreases the sensitivity of the receptor-[35S] TBPS complex to GABA-induced dissociation. GABA at micromolar levels also greatly influences the action of compounds within the TBPS domain, facilitating and modulating displacement of [35S] TBPS from EDTA/water-dialyzed membranes by the alpha-cyanopyrethroid cypermethrin and the barbiturate 5-(1',3'-dimethylbutyl)-5-ethylbarbiturate. Large differences in the Hill numbers indicate that different mechanisms may be involved in GABA modulation of the pyrethroid and barbiturate sites. In contrast, GABA does not effect [35S] TBPS displacement by photoheptachlor epoxide which acts directly at the TBPS binding site. |
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