Effects of propofol, pentobarbital and alphaxalone on t-[35S]butylbicyclophosphorothionate binding in rat cerebral cortex.
The effects of propofol, pentobarbital, alphaxalone, etomidate and diazepam on t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to membrane preparations from rat cerebral cortex were studied in the absence of gamma-aminobutyric acid (GABA). Addition of low concentrations (3-10 microM) of propofol to washed membrane preparations (devoid of GABA) markedly enhanced [35S]TBPS binding (maximal enhancement, 85%), whereas higher concentrations (50-100 microM) 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 a 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 microM) that alone did not modify [35S]TBPS binding (78% increase with 10 microM 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 microM) and alphaxalone (3 microM); etomidate (20 microM) only partially antagonized the effect of propofol. Diazepam at a concentration (30 microM) 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 microM) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Concas
A
A
Department of Experimental Biology, University of Cagliari, Italy.
Santoro
G
G
Mascia
M P
MP
Maciocco
E
E
Dazzi
L
L
Biggio
G
G
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000493:pharmacokinetics*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology; D011277:Pregnanediones / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013462:Sulfur Radioisotopes; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000777:Anesthetics; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018118:Chloride Channels; D011277:Pregnanediones; D013462:Sulfur Radioisotopes; D005680:gamma-Aminobutyric Acid; C037476:tert-butylbicyclophosphorothionate; C006477:alphaxalone; D010424:Pentobarbital; D003975:Diazepam; D001640:Bicuculline; D015742:Propofol