title: Regulation of [35S]t-butylbicyclophosphorothionate binding sites in rat brain by GABA, pyrethroid and barbiturate.
abstract: 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.
mesh_terms: D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D066298:In Vitro Techniques; D007306:Insecticides / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D001463:Barbiturates; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007306:Insecticides; D011722:Pyrethrins; D011963:Receptors, GABA-A; C041598:t-butylbicyclophosphorothionate receptor; C017160:cypermethrin; D005680:gamma-Aminobutyric Acid; C037476:tert-butylbicyclophosphorothionate