title: Low-affinity gamma-aminobutyric acid transport in rat brain.
abstract: The low-affinity (Km = 100-200 microM) gamma-aminobutyric acid (GABA) transporter from membrane vesicles from rat brain has been characterized and found to be in many aspects similar to the well-known sodium- and chloride-coupled high-affinity gamma-aminobutyric acid transporter (Km = 2-4 microM). Influx by this system is sodium and chloride dependent and stimulated by an interior negative membrane potential. Steady-state levels obtained by both systems are lowered by the sodium channel openers veratridine and aconitine. However, while the channel blocker tetrodotoxin fully reverses this inhibition with the high-affinity system, this is not the case for its low-affinity counterpart. Furthermore, the toxin from the scorpion Androctonus australis Hector inhibited high-affinity transport only. Efflux of gamma-aminobutyric acid taken up by the high-affinity system displayed a Km of about 100 microM. Exchange catalyzed by the low-affinity system was observed in the absence of external sodium and chloride. Furthermore, both activities copurified in the fractionation procedure developed to purify the high-affinity transporter. All these observations are consistent with the idea that both activities are manifestations of only one gamma-aminobutyric acid transporter. The high-affinity binding site represents the extracellular and the low-affinity site the cytosolic aspect of the transporter. In addition, it was found that right-side-out synaptosomes also contain a low-affinity GABA transporter. This apparently represents a different transport protein.
authors.affiliation: Department of Biochemistry, Hadassah Medical School, Hebrew Universty, Jerusalem, Israel.
authors.forename: N J
authors.initials: NJ
authors.lastname: Mabjeesh
authors.forename: B I
authors.initials: BI
authors.lastname: Kanner
mesh_terms: D000818:Animals; D001692:Biological Transport; D001923:Brain Chemistry / Q000187:drug effects*; D018756:GABA Antagonists; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D012965:Sodium Chloride / Q000493:pharmacokinetics*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014118:Toxins, Biological / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000302:isolation & purification / Q000493:pharmacokinetics*
chemical_list: D018756:GABA Antagonists; D014118:Toxins, Biological; D013779:Tetrodotoxin; D012965:Sodium Chloride; D005680:gamma-Aminobutyric Acid; D010042:Ouabain