Ligand-dependent effects of ethanol and diethylether at brain benzodiazepine receptors

Pharmacology, Biochemistry, and Behavior
J J Quinlan, L L Firestone

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.

Citations

Apr 21, 1977·Nature·R F Squires, C Brastrup
Jun 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·P D SuzdakS M Paul
May 1, 1987·Medical Hypotheses·S C Cheng, E A Brunner
Dec 30, 1983·Neuroscience Letters·J H Skerritt, R L Macdonald
Dec 24, 1981·Nature·H Möhler, J G Richards
Apr 1, 1984·Journal of Neurochemistry·D A GreenbergI Diamond

Related Concepts

Ethanol
Tissue Membrane
Derivatives
Ethanol Measurement
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Antagonist Muscle Action
Benzodiazepine [EPC]
Benzodiazepine Antagonists
Chloride Channel Complex
Sedatives

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