Journal of Applied Physiology, Vol 73, Issue 6 2552-2558, Copyright © 1992 by American Physiological Society
Brain glutamate metabolism during metabolic alkalosis and acidosis
R. C. Ang, B. Hoop and H. Kazemi
Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
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.
