Effects of propofol, pentobarbital and alphaxalone on [formula omitted] binding in rat cerebral cortex

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The effects of propofol, pentobarbital, alphaxalone, etomidate and diazepam on t[ 35 S] butylbicyclophosphorpthionate ([ 35S]TBPS) binding to membrane preparations from rat cerebral cortex were studied in the absence of γ-aminobutyric acid (GABA). Addition of low concentrations (3–10 μM) of profolol to washed membrane preparations (devoid of GABA) markedly enhanced [ 35S]TBPS binding (maximal enhancement, 85%), whereas higher concentrations (50–100 μM) inhibited this parameter. Diazepam also enhanced [ 35S]TBPS binding in this preparation (maximal enhancement, 38%). In contrast, pentobarbital, alphaxalone and etomidate decreased [ 35S]TBPS binding in concentration-dependent manner. The propofol-induced increase in [ 35S]TBPS binding in washed membranes was completely reversed by the addition of GABA at a concentration (0.3 μM) that alone did not modify [ 35S]TBPS binding (78% increase with 10 μM propofol alone, 33% decrease in the additional presence of GABA). The ability of GABA to reverse the effect of propofol on [ 35S]TBPS binding in washed membranes was shared by pentobarbital (200 μM) and alphaxalone (3 μM); etomidate (20 μM) only partially antagonized the effect of propofol. Diazepam at a concentration (30 μM) that alone had no effect on [ 35S]TBPS binding failed to modify the propofol-induced increase in [ 35S]TBPS binding, whereas at a concentration (3 μM) that alone increased [ 35S]TBPS binding the effect of diazepam was additive with that of propofol. The addition of bicuculline to washed membranes failed to abolish the increase in [ 35S]TBPS binding induced by propofol or diazepam, but completely antagonized the effects of pentobarbital, alphaxalone and etomidate. Moreover, propofol and diazepam further enhanced the bicuculline-induced increase in [ 35S]TBPS binding in unwashed membranes. Our data thus show that, by assaying [ 35S]TBPS binding in washed membranes, it is possible to differentiate the molecular action of propofol from that of other general anesthetics.