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Effects of Ammonia and β‐Methylene‐dl‐Aspartate on the Oxidation of Glucose and Pyruvate by Neurons and Astrocytes in Primary Culture
Author(s) -
Fitzpatrick Susan M.,
Cooper Arthur J. L.,
Hertz Leif
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb03087.x
Subject(s) - phosphocreatine , ammonium chloride , astrocyte , incubation , glutamate receptor , ammonium , biochemistry , chemistry , metabolism , medicine , oxidative phosphorylation , endocrinology , pyruvic acid , biology , energy metabolism , central nervous system , receptor , organic chemistry
Both ammonia and β‐methylene‐dl‐aspartate (β‐MA), an irreversible inhibitor of aspartate aminotransferase activity and thus of the malate‐aspartate shuttle, were found previously to decrease oxidative metabolism in cerebral cortex slices. In the present work, the possibility that ammonia and β‐MA affect energy metabolism by a common mechanism (i.e., via inhibition of the malate‐aspartate shuttle) was investigated using primary cultures of neurons and astrocytes. Incubation of astrocytes for 30 min with 5 m M β‐MA resulted in a decreased production of 14 CO 2 from [U‐ 14 Clglucose, but did not affect 14 CO 2 production from [2– 14 C] pyruvate. Conversely, incubation of astrocytes with 3 m M ammonium chloride resulted in decreased 14 CO 2 production from [2– 14 C] pyruvate, but 14 CO 2 production from [U‐ 14 C] glucose was not significantly affected. Ammonium chloride had no significant effect on 14 CO 2 production from either [U‐ 14 C] glucose or [2– 14 ]pyruvate by neurons. However, incubation of neurons with β‐MA or β‐MA plus ammonium chloride resulted in a 45% decrease of 14 CO 2 production from both [U‐ 14 C] glucose and [2– 14 C] pyruvate. A 2‐h incubation of astrocytes with β‐MA resulted in no change in ATP levels, but a 35% decrease in phosphocreatine. Similar treatment of neurons resulted in >50% decrease in ATP, but had little effect on phosphocreatine. β‐MA also caused a decrease in glutamate and aspartate content of neurons, but not of astrocytes. The different metabolic responses of neurons and astrocytes towards β‐MA were probably not due to a differential inhibition of aspartate aminotransferase which was inhibited by ∼45% in astrocytes and by ∼55% in neurons.