The Picrotoxinin Binding Site and Its Relationship to the GABA Receptor Complex |
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| Authors: | W F White† S R Snodgrass‡ M A Dichter‡ |
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| Institution: | Department of Neuroscience, Children's Hospital, Boston, Massachusetts, U.S.A.;Department of Nenropathology, Boston, Massachusetts, U.S.A.;Department of Neurology, Harvard Medical School, Boston, Massachusetts, U.S.A. |
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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 gamma-aminobutyric acid (GABA), benzodiazepines, or alterations in the Na+ or Cl- composition of the media had no effect on the binding to the rat brain preparation. However, 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 also investigated. The Hill coefficients for these actions were reciprocal, suggesting that they result from complementary interactions between the binding sites for GABA and picrotoxinin. These data support the association of the picrotoxinin binding site with the postsynaptic GABA receptor complex. |
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| Keywords: | Picrotoxinin Binding GABA |
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