Trans-inhibition of glutamate transport prevents excitatory amino acid-induced glycolysis in astrocytes

Ruth Debernardi, Pierre Magistretti, Luc Pellerin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Previous studies have demonstrated that activation of glutamate transporters promotes glycolysis in astrocytes. Current evidence indicates that compounds such as threo-β-hydroxyaspartate (THA) are both competitive inhibitors and substrates for glutamate transporters. In this study, we have analyzed the effect of THA on excitatory amino acid (EAA) transport and on EAA-induced glycolysis in mouse primary astrocyte cultures. In agreement with previous studies in rat astrocytes, THA competitively inhibited 3H-D-aspartate (3H-D-Asp) uptake with an IC50 of 319 μM (K(i)=36.6 μM). In contrast, it did not prevent D-aspartate-induced 3H-2-deoxyglucose (2DG) uptake in these conditions. Preexposure of cells to THA for at least 15 min revealed another form of glutamate transport inhibition. This effect was concentration-dependent with an apparent IC50 of 47.7 μM and showed kinetic characteristics consistent with a mechanism of trans-inhibition. Preincubation with THA also inhibited D-aspartate-induced 3H-2DG uptake in a concentration-dependent manner with an apparent IC50 of 59.8 μM. Comparison with other transportable analogues reveals that they share with THA the ability to cause trans-inhibition of glutamate transport and to prevent glutamate-stimulated glycolysis; THA, however, is unique in that it has no effect alone on glucose utilization after preexposure. These data indicate that trans-inhibition of glutamate transport may be a mechanism by which certain glutamate transport inhibitors can prevent the stimulation of aerobic glycolysis by glutamate in astrocytes. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)39-46
Number of pages8
JournalBrain Research
Volume850
Issue number1-2
DOIs
StatePublished - Dec 11 1999

Keywords

  • Energy metabolism
  • Glia
  • Glucose utilization
  • Glutamate transporter
  • Non-competitive inhibition

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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