Phenobarbitone binding sites in rat brain synaptosomal membranes.
Phenobarbitone binds to rat brain synaptosomeal membranes at a single class of sites of relatively low affinity (Kd 100 microM) and high density (800 pmol/mg protein). Phenobarbitone can be displaced from these binding sites by a range of substituted barbiturates. For those barbiturates which possess anaesthetic, anticonvulsant or depressant properties, there is an excellent correlation between ability to displace phenobarbitone and ability to enhance the binding of the inhibitory neurotransmitter GABA. On the other hand, convulsant barbiturates are relatively more effective in enhancing GABA binding than would be expected from their ability to displace phenobarbitone. These phenobarbitone binding sites may be involved in the potentiation of GABA-mediated synaptic inhibition by barbiturates, an effect likely to contribute to the pharmacological actions of these substances. These barbiturate sites are distinct from GABA recognition sites and from GABA-activated ionophores, since GABA, bicuculline methochloride, diazepam and picrotoxinin did not influence phenobarbitone binding. Furthermore, extraction of the synaptosomal membranes with Triton X-100 abolishes phenobarbitone binding to the membranes while enhancing GABA binding.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D010634:Phenobarbital / Q000378:metabolism*; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism*; D011963:Receptors, GABA-A; D013574:Synaptosomes / Q000378:metabolism*
D011955:Receptors, Drug; D011963:Receptors, GABA-A; C030975:barbiturate receptor; D010634:Phenobarbital