Pharmacological specificity of synaptosomal and synaptic membrane γ-aminobutyric acid (GABA) transport processes

Amino cyclopentane and amino cyclohexane carboxylic acids were examined as potential inhibitors of γ-aminobutyric acid (GABA) uptake in brain synaptosomes and in synaptic membrane vesicles. The resealed synaptic plasma membrane vesicle preparation was used extensively in determining the potency inhibition of GABA uptake by these agents and in comparing their activities to the activities of various acyclic GABA analogs and to analogs of piperidyl-3-carboxylic acid (nipecotic acid). A number of the cyclic and acyclic GABA analogs also stimulated the carrier-mediated efflux of [ 3b]GABA from preloaded synaptic membrane vesicles, whereas nipecotic acid did not increase the efflux of [ 3H]GABA in a dose-dependent manner. These results suggest that there is a competitive type of interaction of the cyclic and acyclic GABA analogs with membrane uptake carriers and that a more complex type of action of nipecotic acid on these carriers occurs. The order of potency of uptake inhibition by some of these agents was compared with previously published orders of activation of physiologic GABA receptors by these compounds.