title: Ligand-dependent effects of ethanol and diethylether at brain benzodiazepine receptors.
abstract: The GABAA receptor chloride channel complex interacts with various categories of sedatives, including the benzodiazepines, and possibly ethanol and volatile general anesthetics. Thus, specific binding of tritiated derivatives of a benzodiazepine antagonist, flumazenil, and an agonist, flunitrazepam, to rat brain membrane fragments was monitored at equilibrium in the presence and absence of anesthetizing concentrations of ethanol and diethylether. Ethanol produced a concentration-dependent inhibition of [3H]flumazenil binding, which was not reversed by the GABAA receptor competitive antagonist bicuculline, but had no effect on [3H]flunitrazepam binding. Both ethanol and diethylether decreased the affinity of the benzodiazepine site for [3H]flumazenil. These data indicate that ethanol and diethylether have GABA-independent effects at the benzodiazepine sites of the GABAA receptor. These findings are inconsistent with a two-state functional model of the benzodiazepine site and, instead, support a model containing a specific, antagonist-favored conformation.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh, PA 15213.
authors.forename: J J
authors.initials: JJ
authors.lastname: Quinlan
authors.forename: L L
authors.initials: LL
authors.lastname: Firestone
mesh_terms: D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D004986:Ether / Q000494:pharmacology*; D005442:Flumazenil / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D008024:Ligands; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism
chemical_list: D008024:Ligands; D011963:Receptors, GABA-A; D004986:Ether; D000431:Ethanol; D005442:Flumazenil; D005445:Flunitrazepam