title: The recombinant GABA transporter GAT1 is downregulated upon activation of protein kinase C.
abstract: Treatment of human embryonic kidney 293 cells expressing the rat gamma-aminobutyric acid (GABA) transporter 1 (GAT1) with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) was found to decrease the velocity of specific [3H]GABA uptake. This downregulation varied with extracellular GABA concentration and was blocked by the PKC inhibitors 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7) and staurosporine. An about 50% reduction of uptake velocity by PMA treatment was observed at GABA concentrations > 1 microM, whereas only a minor effect was seen at low substrate concentrations. These data indicate that GAT1 activity is downregulated by PKC activation.
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D004622:Embryo, Mammalian; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007668:Kidney; D007700:Kinetics; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014162:Transfection; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D050485:GABA Plasma Membrane Transport Proteins; D007546:Isoquinolines; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D010703:Phorbol Esters; D010879:Piperazines; D011994:Recombinant Proteins; C493413:SLC6A1 protein, human; C493415:Slc6a1 protein, rat; C008876:phorbol-12,13-didecanoate; D005680:gamma-Aminobutyric Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate