By using a series of aminocyclopentane- and aminocyclohexanecarboxylic acids, as well as some naturally occurring amino acids, it was possible to determine some aspects of the spatial topography of the GABA membrane binding and transport sites. The Na-independent GABA binding site was found to have a different spatial topography than the Na-dependent binding site in that trans-3-aminocyclopentanecarboxylic acid (trans-3-ACPC) was 7 times more potent than cis-3-ACPC to inhibit Na-independent binding, but only 1.6 times more potent to inhibit Na-dependent binding. The nerve ending GABA transport site was found to be cis- and trans-3-ACPC. However, the transport site differs from the binding site in that similar to the Na-dependent GABA binding site in that it will accommodate both cis-3-aminocyclohexanecarboxylic acid (cis-3-ACHC) is a potent inhibitor of transport but a weak inhibitor of binding. In addition to the differences in spatial characteristics, differences in the subcellular distribution of Na-independent and Na-dependent binding sites were observed. The former were found primarily in the nerve ending-mitochondrial fraction, while the latter were primarily found in the microsomal fraction.
Bibliographical noteFunding Information:
This study was supported in part by USPHS Grants MH 25487 and DA-00564. H. H. Lob is the recipient of Career Research Scientist Development Award K2-DA-70554.
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