Reduced glucose metabolism enhances the glutamate-evoked release of arachidonic acid from striatal neurons.
Glucose deprivation potentiates the glutamate receptor-evoked release of arachidonic acid from cultured mouse striatal neurons. In this study we investigated whether this potentiation would be modified by the end-products of glycolysis. These enhanced responses were completely reversed by the addition of increasing concentrations of either lactate or pyruvate. This reversal was not due to increased osmolarity as substituting sucrose for lactate or pyruvate did not mimic their effects. In contrast, in the presence of glucose, neither lactate nor pyruvate was effective. Furthermore, these monocarboxylic acids rescued neuronal respiration in the absence of glucose. Inhibiting glycolysis with iodoacetate in the presence of glucose reproduced the potentiated glutamate-evoked release of arachidonic acid observed following glucose deprivation and reduced neuronal respiration to the same extent as that observed in the absence of glucose. All of these effects were overcome by the addition of either lactate or pyruvate. The reversal of the potentiated glutamate-evoked release of arachidonic acid by lactate or pyruvate was inhibited by a specific inhibitor of monocarboxylic acid transport, alpha-cyano-4-hydroxycinnamic acid, suggesting that lactate and pyruvate act intracellularly. Therefore, we propose that the enhanced release of arachidonic acid evoked by glutamate during glucose deprivation results from reduced glycolysis and hence from a depletion of lactate or pyruvate.
Williams
R J
RJ
Chaire de Neuropharmacologie, INSERM U.114, Collège de France, Paris, France.
Maus
M
M
Stella
N
N
Glowinski
J
J
Premont
J
J
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology*; D019344:Lactic Acid / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000494:pharmacology; D019289:Pyruvic Acid / Q000494:pharmacology
D016718:Arachidonic Acid; D019344:Lactic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D019289:Pyruvic Acid; D005947:Glucose