Effects of L-glutamate, D-aspartate, and monensin on glycolytic and oxidative glucose metabolism in mouse astrocyte cultures: further evidence that glutamate uptake is metabolically driven by oxidative metabolism

The hypothesis was tested that oxidative metabolism, mainly fueled by gluta mate itself, provides the energy for active, Na+,K+-ATPase-catalyzed Na+ ex trusion following glutamate uptake in conjunction with Na+. This hypothesis was supported by the following observations: (i) glutamate had either no e ffect or caused a slight reduction in glycolytic rate, measured as deoxyglu cose phosphorylation; (ii) D-aspartate, which is accumulated by the L-gluta mate carrier, but cannot be metabolized by the cells, caused an increase in glycolytic rate; (iii) monensin which, like D-aspartate, stimulates the in tracellular, Na+-activated site of the Na, K-ATPase and thus energy metabol ism, but provides no metabolic substrate, stimulated both glycolysis and gl ucose oxidation; and (iv) oxidation of glucose was potently inhibited by gl utamate, although glutamate is known to stimulate oxygen consumption in pri mary cultures of astrocytes, a combination showing that oxidation of a non- glucose substrate is increased in the presence of glutamate. These findings should be considered in attempts to understand metabolic interactions betw een neurons and astrocytes and regulation of energy metabolism in brain. (C ) 2001 Elsevier Science Ltd. All rights reserved.