FAILURE OF GABAERGIC DRUGS TO MODULATE [H-3] PROPOFOL BINDING IN RAT-BRAIN

[H-3]Propofol was shown to bind to specific sites on rat brain P-2 mem branes. Specific binding in the cerebral cortex constituted 90% of tot al binding and increased linearly with protein concentration. [H-3]Pro pofol bound to two populations of binding sites in rat cerebral cortex (high affinity: K(d)90 nM; B-max 5 pmol/mg protein; low affinity: K-d 2 mu M; B-max 50 pmol/mg protein). [H-3]propofol binding was highest in cerebellum, thalamus, hippocampus, and cortex, and lowest in pons-m edulla, striatum, and spinal cord. Subcellular fractionation revealed [3H]propofol binding to he enriched in synaptosomal fractions of rat c erebral cortex. Trypsin reduced and proteinase K abolished specific [H -3]propofol binding in rat cerebral cortex, suggesting an interaction of propofol with proteins rather than other components of membrane. [H -3]propofol binding appeared to be relatively selective for propofol, the binding of which was not affected by several neurotransmitters and by various drugs that act at the level of GABAergic transmission.