Veratridine- and glutamate-induced release of [3H]-GABA from cultured chick retina cells: possible involvement of a GAT-1-like subtype of GABA transporter.
Four subtypes of GABA carriers (GAT1-GAT4) that transport GABA in a sodium-dependent manner were identified so far. In this report, the sodium-dependent release of GABA was investigated in cultured chick retinal cells. Opening of voltage-sensitive sodium channels by veratridine or activation of non-NMDA glutamate receptors induced the release of GABA from cultured cells. The release of GABA was calcium-independent, but could be completely prevented by the substitution of sodium chloride by lithium or choline chloride in the extracellular medium, suggesting that GABA release could be triggered by multiple mechanisms that led to the flux of sodium into these cells. Pharmacological experiments revealed that, while GABA uptake was almost completely inhibited by the GAT-1 blockers NNC-711 (50 microM) or nipecotic acid (1 mM), the release of this amino acid was inhibited by NNC-711, but not by nipecotic acid. The incubation with beta-alanine (10 mM), a GAT-2/GAT-3 inhibitor, blocked 50% of GABA uptake but had no effect on the release. Our data suggest that sodium-dependent GABA release from cultured chick retina cells is mediated by a GAT-1 like transporter that shows some, but not all, the pharmacological properties of the GAT-1 carrier.
Department of Physiology, Federal University of Pará, Belém, PA, Brazil.
J L
JL
do Nascimento
A L
AL
Ventura
R
R
Paes de Carvalho
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000494:pharmacology*; D008565:Membrane Proteins / Q000502:physiology*; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D014701:Veratridine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002352:Carrier Proteins; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D014316:Tritium; D018698:Glutamic Acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D014701:Veratridine