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Abstract

Anesthetic and convulsant barbiturates alter gamma-aminobutyric acid-stimulated chloride flux across brain membranes.

A M Allan and R A Harris
Journal of Pharmacology and Experimental Therapeutics September 1986, 238 (3) 763-768;
A M Allan
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R A Harris
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Abstract

gamma-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain, increases membrane chloride conductance. Previously, the authors reported that GABA increases 36Cl- uptake by membrane vesicles (microsacs) prepared from mouse brain. In the present study, we examined the actions of barbiturates on basal and GABA-stimulated chloride influx by brain vesicles. The anesthetic barbiturates pentobarbital, phenobarbital, mephobarbital, amobarbital, hexobarbital and R-(-)-1-methyl-5-phenyl-5-propyl barbiturate enhanced GABA-dependent chloride flux. Barbiturate enhancement of GABA action was seen at concentrations that are subanesthetic in vivo (e.g., 10 microM pentobarbital was effective). Pentobarbital was about 10 times more potent than pentobarbital, suggesting that chloride flux is related to the sedative rather than anticonvulsant actions of barbiturates. Pentobarbital (1 mM) prevented the antagonism of GABA-stimulated 36Cl- produced by picrotoxinin. The barbiturates generally produced no change in GABA-independent flux, although large concentrations of pentobarbital or hexobarbital produced a slight enhancement of chloride flux in the absence of GABA. The convulsant barbiturate S-(+)-1-methyl-5-phenyl-5-propyl barbiturate inhibited GABA-stimulated chloride flux, an action opposite to that of its anesthetic enantiomer. These experiments provide evidence for a functional coupling among GABA and barbiturate receptors and the chloride ionophore and suggest that the GABA-activated chloride channel is a site of action for intoxicant-anesthetic and convulsant barbiturates.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 238, Issue 3
1 Sep 1986
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Abstract

Anesthetic and convulsant barbiturates alter gamma-aminobutyric acid-stimulated chloride flux across brain membranes.

A M Allan and R A Harris
Journal of Pharmacology and Experimental Therapeutics September 1, 1986, 238 (3) 763-768;

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Abstract

Anesthetic and convulsant barbiturates alter gamma-aminobutyric acid-stimulated chloride flux across brain membranes.

A M Allan and R A Harris
Journal of Pharmacology and Experimental Therapeutics September 1, 1986, 238 (3) 763-768;
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