Lindane inhibition of [ 35S]TBPS binding to the GABA A receptor in rat brain

Abstract

The inhibition of [ 35S]t-butylbicyclophosphorothionate ([ 35S]TBPS) binding to the GABA A receptor by the insecticide γ-hexachlorocyclohexane, lindane, was studied in several brain regions and using different membrane preparation methods, both in vitro and after dosing the animals with the chemical. In the latter studies, the amount of lindane remaining in the membrane suspensions used for binding assays was determined. In vitro data showed values of IC 50 from 150 to 1675 nM, varying in function of the membrane preparation method used. This may account for the discrepancies in IC 50 values found in the literature. IC 50 values within the range of 150–250 nM were determined using extensively washed membranes from several brain regions, so no evidence arose for brain regional differences in the affinity of lindane for the TBPS binding site. After different schedules of acute treatment with lindane, we found a manifest relationship between the extent of the observable inhibition of [ 35S]TBPS binding and the lindane amount remaining in the membrane suspensions used for binding assays. This relationship was in good agreement with the in vitro data, so no support for an in vivo acute regulation of the binding site was obtained.