Modulation of the GABA receptor complex by a steroid anaesthetic.
The interactions of a steroid anaesthetic, alphaxalone, with the GABA receptor-ionophore complex were investigated by two different experimental approaches. In the rat cuneate nucleus slice, alphaxalone (0.1-10 microM) potentiated depolarizing responses to superfused GABA and muscimol, but not those to glycine. The potentiating effect of alphaxalone was unaltered by the benzodiazepine antagonist Ro 15-1788. Alphaxalone (0.1-30 microM) also enhanced [3H]muscimol binding to rat brain membranes in the presence of Cl-ions; the enhancing effect on [3H]muscimol binding was abolished by Triton X-100. Analysis of binding curves for [3H]muscimol indicated that the steroid anaesthetic increases the affinity for [3H]muscimol of low affinity binding sites; this property is shared by pentobarbitone. The physiologically inactive beta-hydroxy isomer of the steroid was without activity in either of the experimental situations at 30 microM. It is suggested that alphaxalone and pentobarbitone share a common mode of action on the GABA system, which may be relevant to the mechanisms by which these drugs produce anaesthesia.
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D009118:Muscimol / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology; D011277:Pregnanediones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects
D000777:Anesthetics; D011277:Pregnanediones; D011942:Receptors, Adrenergic, alpha; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D009118:Muscimol; C006477:alphaxalone; D010424:Pentobarbital