The Picrotoxinin Binding Site and Its Relationship to the GABA Receptor Complex

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Abstract
The binding characteristics of [3H].alpha.-dihydropicrotoxinin to the picrotoxinin binding site were investigated in membrane preparations of adult rat forebrain and living cultures of rat cerebral cortex. The binding of [3H].alpha.-dihydropicrotoxinin to rat forebrain was decreased by lysing, treating with Triton X-100 and heating. Coincubation with GABA, benzodiazepines or alterations in the Na+ or Cl- composition of the media had no effect on the binding to the rat brain preparation. In the living neurons in tissue culture both GABA and diazepam significantly decreased the binding of [3H].alpha.-dihydropicrotoxinin. The dose-response relationships for GABA antagonism of [3H].alpha. dihydropicrotoxinin binding and for picrotoxinin antagonism of the GABA enhancement of [3H]flunitrazepam binding in cultured cortical neurons were investigated. The Hill coefficients for these actions were reciprocal, suggesting that they result from complementary interactions between the binding sites for GABA and picrotoxinin. The picrotoxinin binding site is apparently associated with the postsynaptic GABA receptor complex.