Differential effects of sedative and anticonvulsant barbiturates on specific [3H]GABA binding to membrane...

The sensitivity to barbiturates of [3H]GABA binding to synaptosomal membrane fractions from rat cortex has been examined. We show that a range of anaesthetic/sedative barbiturates enhance GABA binding in the presence of chloride or other ions that interact with the associated ionophore. Furthermore, picrotoxinin and the anticonvulsant barbiturate phenobarbital antagonise the enhancement produced by pentobarbital. These effects are therefore comparable to those observed at benzodiazepine receptors and may be mediated through the chloride ionophore component of the receptor complex. Other classes of anticonvulsants failed to antagonise pentobarbital activation, suggesting that these interactions may occur at a specific barbiturate site in the membrane.