Metabolic Effects of Blocking Lactate Transport in Brain Cortical Tissue Slices Using an Inhibitor Specific to MCT1 and MCT2 |
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Authors: | Caroline Rae Fatima A Nasrallah Stefan Bröer |
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Institution: | (1) Prince of Wales Medical Research Institute, Barker St., Randwick, NSW, 2031, Australia;(2) Brain Sciences UNSW, The University of New South Wales, Sydney, NSW, 2052, Australia;(3) School of Biochemistry and Molecular Biology, Australian National University, Acton, ACT, 0200, Australia |
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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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Keywords: | 13C NMR spectroscopy Astrocyte-neuron lactate shuttle hypothesis Monocarboxylate transporter Brain metabolism Lactic acid |
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