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 stud y we investigated whether this potentiation would be modified by the e nd-products of glycolysis. These enhanced responses were completely re versed by the addition of increasing concentrations of either lactate or pyruvate. This reversal was not due to increased osmolarity as subs tituting 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 neurona l respiration in the absence of glucose. Inhibiting glycolysis with io doacetate in the presence of glucose reproduced the potentiated glutam ate-evoked release of arachidonic acid observed following glucose depr ivation and reduced neuronal respiration to the same extent as that ob served in the absence of glucose. All of these effects were overcome b y the addition of either lactate or pyruvate. The reversal of the pote ntiated glutamate-evoked release of arachidonic acid by lactate or pyr uvate was inhibited by a specific inhibitor of monocarboxylic acid tra nsport, alpha-cyano-4-hydroxycinnamic acid, suggesting that lactate an d pyruvate act intracellularly. Therefore, we propose that the enhance d release of arachidonic acid evoked by glutamate during glucose depri vation results from reduced glycolysis and hence from a depletion of l actate or pyruvate. Copyright (C) 1996 IBRO. Published by Elsevier Sci ence Ltd.