Stimulation of deoxy[3H]glucose uptake into slices from cerebral cortex elicited by excitatory amino acids

Slices from rat cerebral cortex incubated in the presence of 2-deoxy[3H]glucose accumulate the sugar mainly in the form of its phosphorylated derivative. 2-Deoxy[3H]glucose uptake, measured under conditions of initial velocity, is stimulated by 50-100% in the presence of depolarising agents (KCl, veratridine) or the excitatory amino acids L- and D-glutamate, L-aspartate and L-cysteate in millimolar concentrations. In contrast a variety of putative neurotransmitters are ineffective on this test. The stimulations elicited by KCl or excitatory amino acids consist in significant increases in both the apparent Km and Vmax values of the 2-deoxyglucose transport system. The effect of excitatory amino acids is not significantly modified in the presence of tetrodotoxin or when the extracellular Ca2+ concentration is diminished, whereas it is significantly reduced in the presence of ouabain. Hence stimulation of 2-deoxy[3H]glucose uptake and phosphorylation may indirectly reflect the activation of Na+, K+-adenosine 5'-triphosphatases triggered by excitatory amino acids in target cells. The stimulation of 2-deoxy[3H]glucose uptake elicited by the three excitatory amino acids is antagonised in an apparently competitive manner by glutamate diethyl ester (apparent Ki value of congruent to 15 mM) whereas the KCl-induced stimulation is not modified. In contrast a variety of other amino acid agonists (including quisqualate, kainate, N-methyl D-aspartate) or antagonists (including gamma-D-glutamyl glycine acid and 2-amino-5-phosphonovalerate) are inactive, indicating that the metabolic response is not mediated by any of the receptor subclasses identified electrophysiologically.