Activation of high-affinity uptake of glutamate by phorbol esters in primary glial cell cultures.
The effects of 12-O-tetradecanoylphorbol 13-acetate (TPA), a potent activator of protein kinase C, on high-affinity Na(+)-dependent glutamate transport were investigated in primary cultures of neurons and glial cells from rat brain cortex. Incubation of glial cells with TPA led to concentration- and time-dependent increases in the glutamate transport that could be completely suppressed by the addition of the protein kinase C (PKC) inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine. The TPA effects could be mimicked by oleoylacetylglycerol and by the diacylglycerol kinase inhibitor R59022. The effects of TPA were potentiated by the Ca2+ ionophore A23187. Under the chosen experimental conditions TPA had no effect on glutamate transport in neurons. We conclude that PKC activates the sodium-dependent high-affinity glutamate transport in glial cells and that it has dissimilar effects on neurons and glial cells.
Centro de Biología Molecular, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
M
M
Casado
F
F
Zafra
C
C
Aragón
C
C
Giménez
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001667:Binding, Competitive; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D004075:Diglycerides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005971:Glutamates / Q000493:pharmacokinetics*; D018698:Glutamic Acid; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004075:Diglycerides; D005971:Glutamates; D007546:Isoquinolines; D010879:Piperazines; D000001:Calcimycin; D018698:Glutamic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C038237:1-oleoyl-2-acetylglycerol; D013755:Tetradecanoylphorbol Acetate