Pentobarbital and synaptic high-affinity receptive sites for gamma-aminobutyric acid.

Electrophysiological investigations of others show that pentobarbital enhances the inhibitory inflences of gamma-aminobutyric acid (GABA). Specifically, receptor activation is amplified and prolonged, suggesting the presence of an increased number of GABA molecules in the synaptic cleft. Either inactivation of high-affinity GABA transport or alteration of post-synaptic GABA receptors might account for these influences of pentobarbital. In this sudy the effect of pentobarbital on high-affinity uptake and binding of GABA to synaptic receptive sites has been examined. Using synaptosomes and subsynaptosomal fractions of cerebral cortex and hippocampus, it si shown that concentrations of pentobarbital, exceeding 1 mM have no appreciable effect on GABA uptake or binding. Thus the synaptic influence of pentobarbital, evident at 0.1 mM in electrophysiologic experiments, must originate from mechanisms other than the high-affinity uptake or binding of GABA. Possible sites of action include the presynaptic release of GABA and the ionophores coupled with postsynapitc sites.