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Metabolic Effects of Blocking Lactate Transport in Brain Cortical Tissue Slices Using an Inhibitor Specific to MCT1 and MCT2

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Abstract

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-[3-13C]lactate, and d-[1-13C]glucose under a range of conditions. Experiments using l-[3-13C]lactate showed that the inhibitor AR-C122982 altered exchange of lactate. Under depolarizing conditions, net flux of label from d-[1-13C]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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Acknowledgments

This work was supported by the University of New South Wales and NewSouth Global (UNSW) and the Australian National Health and Medical Research Council (grant to CR). The authors are grateful to the staff of the UNSW Analytical Centre for expert technical assistance.

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Authors and Affiliations

  1. Prince of Wales Medical Research Institute, Barker St., Randwick, NSW, 2031, Australia

    Caroline Rae & Fatima A. Nasrallah

  2. Brain Sciences UNSW, The University of New South Wales, Sydney, NSW, 2052, Australia

    Caroline Rae

  3. School of Biochemistry and Molecular Biology, Australian National University, Acton, ACT, 0200, Australia

    Stefan Bröer

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  1. Caroline Rae
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Correspondence to Caroline Rae.

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Rae, C., Nasrallah, F.A. & Bröer, S. Metabolic Effects of Blocking Lactate Transport in Brain Cortical Tissue Slices Using an Inhibitor Specific to MCT1 and MCT2. Neurochem Res 34, 1783–1791 (2009). https://doi.org/10.1007/s11064-009-9973-0

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