Further studies on the effects of topical lactate on amino acid efflux from the ischemic rat cortex

Further studies on the effects of topical lactate on amino acid efflux from the ischemic rat cortex A rat four-vessel cerebral occlusion model was used to examine the effects of d -lactate and oxamate, a lactate dehydrogenase inhibitor, on cortical window superfusate levels of amino acids, glucose and l -lactate. Superfusate levels of aspartate, glutamate, taurine, GABA and phosphoethanolamine rose during ischemia and then declined during reperfusion. Glycine and alanine levels tended to increase during reperfusion, whereas glutamine levels were lower. Serine levels were not altered. Glucose levels declined rapidly during ischemia and recovered during reperfusion. Lactate levels were sustained during ischemia and increased during reperfusion. Unlike l -lactate, which attenuated ischemia/reperfusion (I/R) evoked amino acid release (J.W. Phillis, D. Song, L.L. Guyot, M.H. O’Regan, Lactate reduces amino acid release and fuels recovery of function in the ischemic brain, Neurosci. Lett. 272 (1999) 195–198), topical application of d -lactate (20 mM), which is not used as an energy substrate, enhanced the I/R release of aspartate, glutamate, GABA and taurine into cortical superfusates, and also elevated l -lactate levels above those in the controls. Glucose levels were not altered. Oxamate (20 mM) application elevated the pre-ischemia levels of alanine, glycine and GABA and those of GABA during ischemia. Levels of all amino acids, with the exception of phosphoethanolamine, were elevated during reperfusion. Oxamate, an inhibitor of lactate dehydrogenases 1 and 5, did not alter the pattern of efflux of glucose and l -lactate. In the presence of oxamate, l -lactate (20 mM) failed to inhibit amino acid release. The failure of d -lactate to attenuate amino acid release confirms the inability of this isomer to act as a metabolic substrate. The oxamate data indicate that inhibition of lactate dehydrogenase is detrimental to the viability of cortical cells during I/R, even though extracellular lactate levels are elevated. The pre-ischemia increases in alanine and glycine are suggestive of elevations in pyruvate as a result of the block of its conversion to lactate, with transamination reactions converting pyruvate to form these amino acids. In summary, the results further substantiate the concept of a role for l -lactate as a cerebral energy substrate. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Further studies on the effects of topical lactate on amino acid efflux from the ischemic rat cortex

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Publisher
Elsevier
Copyright
Copyright © 2001 Elsevier Science B.V.
ISSN
0006-8993
D.O.I.
10.1016/S0006-8993(01)02183-7
Publisher site
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Abstract

A rat four-vessel cerebral occlusion model was used to examine the effects of d -lactate and oxamate, a lactate dehydrogenase inhibitor, on cortical window superfusate levels of amino acids, glucose and l -lactate. Superfusate levels of aspartate, glutamate, taurine, GABA and phosphoethanolamine rose during ischemia and then declined during reperfusion. Glycine and alanine levels tended to increase during reperfusion, whereas glutamine levels were lower. Serine levels were not altered. Glucose levels declined rapidly during ischemia and recovered during reperfusion. Lactate levels were sustained during ischemia and increased during reperfusion. Unlike l -lactate, which attenuated ischemia/reperfusion (I/R) evoked amino acid release (J.W. Phillis, D. Song, L.L. Guyot, M.H. O’Regan, Lactate reduces amino acid release and fuels recovery of function in the ischemic brain, Neurosci. Lett. 272 (1999) 195–198), topical application of d -lactate (20 mM), which is not used as an energy substrate, enhanced the I/R release of aspartate, glutamate, GABA and taurine into cortical superfusates, and also elevated l -lactate levels above those in the controls. Glucose levels were not altered. Oxamate (20 mM) application elevated the pre-ischemia levels of alanine, glycine and GABA and those of GABA during ischemia. Levels of all amino acids, with the exception of phosphoethanolamine, were elevated during reperfusion. Oxamate, an inhibitor of lactate dehydrogenases 1 and 5, did not alter the pattern of efflux of glucose and l -lactate. In the presence of oxamate, l -lactate (20 mM) failed to inhibit amino acid release. The failure of d -lactate to attenuate amino acid release confirms the inability of this isomer to act as a metabolic substrate. The oxamate data indicate that inhibition of lactate dehydrogenase is detrimental to the viability of cortical cells during I/R, even though extracellular lactate levels are elevated. The pre-ischemia increases in alanine and glycine are suggestive of elevations in pyruvate as a result of the block of its conversion to lactate, with transamination reactions converting pyruvate to form these amino acids. In summary, the results further substantiate the concept of a role for l -lactate as a cerebral energy substrate.

Journal

Brain ResearchElsevier

Published: May 18, 2001

References

  • Carrier mediated transport of lactic acid in cultured neurons and astrocytes
    Nedergaard, M.; Goldman, S.A.
  • Mechanisms of glutamate and aspartate release in the ischemic rat cerebral cortex
    Phillis, J.W.; O’Regan, M.H.
  • 5-(N-ethyl-N-isopropyl)-amiloride inhibits amino acid release from the ischemic rat cerebral cortex: role of Na + -H + exchange
    Phillis, J.W.; O’Regan, M.H.; Song, D.
  • Inhibition of Na + /H + exchange by 5-(N-ethyl-N-isopropyl)-amiloride reduces free fatty acid efflux from the ischemic reperfused rat cerebral cortex
    Phillis, J.W.; Ren, J.; O’Regan, M.H.
  • Lactate reduces amino acid release and fuels recovery of function in the ischemic brain
    Phillis, J.W.; Song, D.; Guyot, L.L.; O’Regan, M.H.
  • Transport of lactate and other monocarboxylates across mammalian plasma membranes
    Poole, R.C.; Halestrap, A.P.
  • Brain lactate, not glucose, fuels the recovery of synaptic function from hypoxia upon reoxygenation: an in vitro study
    Schurr, A.; Payne, R.S.; Miller, J.J.; Rigor, B.M.
  • Lactate release from cultured astrocytes and neurons: a comparison
    Walz, W.; Muckerji, S.
  • Selective inhibition of the sperm-specific lactate dehydrogenase isozyme-C4 by N-isopropyl oxamate
    Wong, C.; Rodriguez-Paez, L.; Nogueda, B.; Perez, A.; Baeza, I.

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