The recombinant GABA transporter GAT1 is downregulated upon activation of protein kinase C

FEBS Lett. 1995 Nov 13;375(1-2):99-102. doi: 10.1016/0014-5793(95)01191-g.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Alkaloids / pharmacology
  • Animals
  • Biological Transport / drug effects
  • Carrier Proteins / drug effects
  • Carrier Proteins / metabolism*
  • Cell Line
  • Embryo, Mammalian
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • GABA Plasma Membrane Transport Proteins
  • Humans
  • Isoquinolines / pharmacology
  • Kidney
  • Kinetics
  • Membrane Proteins / drug effects
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins*
  • Organic Anion Transporters*
  • Phorbol Esters / pharmacology
  • Piperazines / pharmacology
  • Protein Kinase C / metabolism*
  • Rats
  • Recombinant Proteins / drug effects
  • Recombinant Proteins / metabolism
  • Staurosporine
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Transfection
  • gamma-Aminobutyric Acid / metabolism*
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Alkaloids
  • Carrier Proteins
  • Enzyme Inhibitors
  • GABA Plasma Membrane Transport Proteins
  • Isoquinolines
  • Membrane Proteins
  • Membrane Transport Proteins
  • Organic Anion Transporters
  • Phorbol Esters
  • Piperazines
  • Recombinant Proteins
  • SLC6A1 protein, human
  • Slc6a1 protein, rat
  • phorbol-12,13-didecanoate
  • gamma-Aminobutyric Acid
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Protein Kinase C
  • Staurosporine
  • Tetradecanoylphorbol Acetate