Two pharmacologically distinct sodium- and chloride-coupled high-affinity gamma-aminobutyric acid transporters are present in plasma membrane vesicles and reconstituted preparations from rat brain.

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Abstract
Electrogenic sodium- and chloride-dependent .gamma.-aminobutyric acid (GABA) transport in crude synaptosomal membrane vesicles is partly inhibited by saturating levels of either of the substrate analogues cis-3-aminocyclohexanecarboxylic acid (ACHC) or .beta.-alanine. However, both of them together potently and fully inhibit the process. Transport of .beta.-alanine, which exhibits an apparent Km of about 44 .mu.M, is also electrogenic and sodium and chloride dependent and competitively inhibited by GABA with a Ki of about 3 .mu.M. This value is very similar to the Km of 2-4 .mu.M found for GABA transport. On the other hand, ACHC does not inhibit .beta.-alanine transport at all. Upon solubilization of the membrane proteins with cholate and fractionation with ammonium sulfate, a fraction is obtained which upon reconstitution into proteoliposomes exhibits 4- to 10-fold-increased GABA transport. This activity is fully inhibited by low concentrations of ACHC and is not sensitive at all of .beta.-alanine. GABA transport in this preparation exhibits an apparent Km of about 2.5 .mu.M and its is competitively inhibited by ACHC (Ki .apprxeq. 7 .mu.M). These data indicate the presence of two GABA transporter subtypes in the membrane vesicles: the A type, sensitive to ACHC, and the B type, sensitive to .beta.-alanine.

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