A gamma-aminobutyric acid-specific transport mechanism in mammalian kidney.
We describe high-affinity, sodium-dependent transport of gamma-aminobutyric acid in slices exposing basal lateral membranes and brush-border membrane vesicles prepared from rat renal cortex. In the presence of aminooxyacetic acid, to block gamma-aminobutyric acid oxidation, uptake into the intracellular space of slices was saturable (apparent Kt, 26 +/- 4 microM, mean and S.E.) and concentrative (steady-state distribution ratio at 50 microM gamma-aminobutyric acid, 47.7 +/- 2.4, mean and S.E.). Brush-border membrane vesicles accumulated gamma-aminobutyric acid in the presence of an inward-directed sodium chloride gradient, (apparent Kt, 30-36 microM) with the peak of 'overshoot' at 10 min. Uptake by vesicles responded to manipulation of the transmembrane potential gradient with valinomycin or impermeant anion. beta-Alanine inhibited gamma-aminobutyric acid transport by slices and brush-border membrane vesicles; inhibitors of neuronal-type gamma-aminobutyric acid transport (e.g., nipecotic and diaminobutyric acids) did not. An 'ABC test' indicated that gamma-aminobutyric acid and beta-alanine do not share a single carrier in either the brush-border or basal-lateral membrane of renal cortex. Influx of gamma-aminobutyric acid into brush-border membrane vesicles, at transequilibrium NaCl, was stimulated by trans-gamma-aminobutyric acid but not by trans-taurine. Ion gradient-driven gamma-aminobutyric acid co-transport was unaffected in freeze-thawed brush-border membrane vesicles; this treatment abolished beta-alanine and taurine co-transport. We conclude that rat kidney membranes (brush-border and basal-lateral) possess a gamma-aminobutyric acid-preferring, high-affinity transport mechanism.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D015091:beta-Alanine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D015091:beta-Alanine; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D010130:p-Aminohippuric Acid