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 [H-3]GABA uptake. This downregulatio
n varied with extracellular GABA concentration and was blocked by the
PKC inhibitors 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7) an
d staurosporine. An about 50% reduction of uptake velocity by PMA trea
tment was observed at GABA concentrations >1 mu M, whereas only a mino
r effect was seen at low substrate concentrations, These data indicate
that GAT1 activity is downregulated by PKC activation.