Journal
NEUROCHEMICAL RESEARCH
Volume 34, Issue 10, Pages 1783-1791Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-009-9973-0
Keywords
(13)C NMR spectroscopy; Astrocyte-neuron lactate shuttle hypothesis; Monocarboxylate transporter; Brain metabolism; Lactic acid
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Funding
- University of New South Wales and NewSouth Global (UNSW)
- Australian National Health and Medical Research Council
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A novel inhibitor of lactate transport, AR-C122982, was used to study the effect of inhibiting the monocarboxylate transporters MCT1 and MCT2 on cortical brain slice metabolism. We studied metabolism of l-[3-(13)C]lactate, and d-[1-(13)C]glucose under a range of conditions. Experiments using l-[3-(13)C]lactate showed that the inhibitor AR-C122982 altered exchange of lactate. Under depolarizing conditions, net flux of label from d-[1-(13)C]glucose was barely altered by 10 or 100 nM AR-C122982. In the presence of AMPA or glutamate there were increases in net flux of label and metabolic pool sizes. These data suggest lactate may supply compartments in the brain not usually directly accessed by glucose. In general, it would appear that movement of lactate between cell types is not essential for metabolic activity, with the heavy metabolic workloads imposed being unaffected by inhibition of MCT1 and MCT2. Further experiments investigating the mechanism of operation of AR-C122982 are necessary to corroborate this finding.
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