Modulation of the GABAA-like autoreceptor by barbiturates but not by steroids.
In slices of cerebral cortex from rat preloaded with [3H]GABA, muscimol produced a concentration-related inhibition of K(+)-evoked release of tritium with a pIC25 value of 7.80 +/- 0.39. Dimethylbarbituric acid (10 and 100 microM) and pentobarbitone (100 microM) significantly increased this value to 8.31 +/- 0.09, 9.91 +/- 0.21 and 8.50 +/- 0.21, respectively, whereas the steroid ligands alphaxalone (1 microM) and 5 beta-pregnane-3 alpha-ol-20-one (10 nM) had no significant effect. The 5 beta-pregnane-3 alpha-ol-20-one and 5 beta-pregnane-3,20-dione produced a concentration-related increase in K(+)-evoked release of tritium alone. These data suggest that the GABAA-like autoreceptor may be modulated by barbiturates but not by steroids and thus may be different from the postsynaptic GABAA receptor.
Wyeth Research (UK) Ltd, Berkshire, U.K.
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D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D011277:Pregnanediones / Q000494:pharmacology; D011278:Pregnanes / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D013256:Steroids / Q000494:pharmacology*
D000777:Anesthetics; D001463:Barbiturates; D011277:Pregnanediones; D011278:Pregnanes; D011963:Receptors, GABA-A; D013256:Steroids; D011189:Potassium Chloride; C006477:alphaxalone