Brain glutamate metabolism during metabolic alkalosis and acidosis.
Glutamate modifies ventilation by altering neural excitability centrally. Metabolic acid-base perturbations may also alter cerebral glutamate metabolism locally and thus affect ventilation. Therefore, the effect of metabolic acid-base perturbations on central nervous system glutamate metabolism was studied in pentobarbital-anesthetized dogs under normal acid-base conditions and during isocapnic metabolic alkalosis and acidosis. Cerebrospinal fluid transfer rates of radiotracer [13N]ammonia and of [13N]glutamine synthesized de novo via the reaction glutamate+NH3-->glutamine in brain glia were measured during normal acid-base conditions and after 90 min of acute isocapnic metabolic alkalosis and acidosis. Cerebrospinal fluid [13N]ammonia and [13N]glutamine transfer rates decreased in metabolic acidosis. Maximal glial glutamine efflux rate jm equals 85.6 +/- 9.5 (SE) mumol.l-1 x min-1 in all animals. No difference in jm was observed in metabolic alkalosis or acidosis. Mean cerebral cortical glutamate concentration was significantly lower in acidosis [7.01 +/- 0.45 (SE) mumol/g brain tissue] and tended to be larger in alkalosis, compared with 7.97 +/- 0.89 mumol/g in normal acid-base conditions. There was a similar change in cerebral cortical gamma-aminobutyric acid concentration. Within the limits of the present method and measurements, the results suggest that acute metabolic acidosis but not alkalosis reduces glial glutamine efflux, corresponding to changes in cerebral cortical glutamate metabolism. These results suggest that glutamatergic mechanisms may contribute to central respiratory control in metabolic acidosis.
Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
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D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000378:metabolism*; D000471:Alkalosis / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004285:Dogs; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000378:metabolism; D009587:Nitrogen Isotopes; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D015656:Respiratory Mechanics / Q000502:physiology
D005971:Glutamates; D009587:Nitrogen Isotopes; D000644:Quaternary Ammonium Compounds; D005973:Glutamine; D018698:Glutamic Acid