Ethanol stimulates γ-aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosomes

P. D. Suzdak, R. D. Schwartz, P. Skolnick, S. M. Paul

Research output: Contribution to journalArticle

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Abstract

The effects of ethanol on Cl- uptake were studied using a cell-free subcellular preparation from brain that contains a γ-aminobutyric acid (GABA)/barbiturate receptor-sensitive Cl- transport system. In isolated vesicles prepared from rat cerebral cortex, ethanol, at concentrations that are present during acute intoxication (20-50 mM), stimulated 36Cl- uptake in a concentration-dependent and biphasic manner. The ethanol-stimulated uptake of 36Cl- was markedly inhibited by the GABA antagonists picrotoxin and bicuculline but not by a variety of other neurotransmitter receptor antagonist. The effects of ethanol in stimulating 36Cl- uptake in isolated brain vesicles were qualitatively and quantitatively similar to that of pentobarbital. Ethanol also markedly potentiated both muscimol- and pentobarbital-stimulated 36Cl- uptake at concentrations below those that directly stimulate 36Cl- uptake. Under our incubation conditions, ethanol did not release GABA, suggesting that it interacts with the postsynaptic GABA/barbiturate receptor complex. The ability of ethanol to stimulate GABA/barbiturate receptor-mediated Cl- transport may explain many of its pharmacological properties and provides a mechanism for the common psychopharmacological actions of ethanol, barbiturates, and benzodiazepines.

Original languageEnglish
Pages (from-to)4071-4075
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume83
Issue number11
DOIs
StatePublished - Jan 1 1986
Externally publishedYes

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