PMID: 8613949Apr 1, 1996Paper

Inhibition of rho1 receptor GABAergic currents by alcohols and volatile anesthetics

The Journal of Pharmacology and Experimental Therapeutics
S J Mihic, R A Harris

Abstract

We studied the effects of alcohols and anesthetics on homomeric gamma-aminobutyric acid (GABA) receptors formed of rho1 subunits expressed in Xenopus laevis oocytes. This subunit shares considerable amino acid sequence homology with the GABA(A) receptor subunits. In contrast to our previous findings with a variety of GABA(A) receptors, ethanol (10-100 mM) significantly inhibited the current induced by a low concentration (400 nM) of GABA, in an apparently competitive manner. Butanol (2-40 mM), hexanol (0.5-4 mM), heptanol (0.3-1 mM), octanol (0.055-1 mM) and nonanol (45 and 113 microM) also inhibited these GABAergic currents. Although efficacious positive modulators of GABA(A) receptor function, the volatile anesthetics enflurane, halothane and isoflurane inhibited the function of rho1 receptors. All of these drug effects were fully reversed by a 6-min washout period. When higher concentrations of GABA were used (5 microM) producing approximately 80-90% of a maximal response) neither the alcohols nor enflurane had any effect. In agreement with previous reports, pentobarbital (50 and 200 microM) was ineffective at any GABA concentration tested. Alphaxalone and propofol were also without effect. Furthermore, none of these compoun...Continue Reading

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