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Differential effects of ammonia and β-methylene-dl-aspartate on metabolism of glutamate and related amino acids by astrocytes and neurons in primary culture

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Abstract

The effects of ammonium chloride (3 mM) and β-methylene-dl-aspartate (BMA; 5 mM) (an inhibitor of aspartate aminotransferase, a key enzyme of the malate-aspartate shuttle (MAS)) on the metabolism of glutamate and related amino acids were studied in primary cultures of astrocytes and neurons. Both ammonia and BMA inhibited14CO2 production from [U-14C]-and [1-14C]glutamate by astrocytes and neurons and their effects were partially additive. Acute treatment of astrocytes with ammonia (but not BMA) increased astrocytic glutamine. Acute treatment of astrocytes with ammonia or BMA decreased astrocytic glutamate and aspartate (both are key components of the MAS). Acute treatment of neurons with ammonia decreased neuronal aspartate and glutamine and did not apparently affect the efflux of aspartate from neurons. However, acute BMA treatment of neurons led to decreased neuronal glutamate and glutamine and apparently reduced the efflux of aspartate and glutamine from neurons. The data are consistent with the notion that both ammonia and BMA may inhibit the MAS although BMA may also directly inhibit cellular glutamate uptake. Additionally, these results also suggest that ammonia and BMA exert differential effects on astroglial and neuronal glutamate metabolism.

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Author notes

  1. Ch. R. K. Murthy

    Present address: School of Life Sciences, University of Hyderabad, 500 134, Hyderabad, AP, India

Authors and Affiliations

  1. Department of Neurology, Cornell University Medical College, 10021, New York, NY

    J. C. K. Lai & A. J. L. Cooper

  2. Department of Pharmacology, University of Saskatchewan, S7N OWO, Saskatoon, Canada

    Ch. R. K. Murthy, E. Hertz & L. Hertz

  3. Biochemistry Department (Rm E0025), Cornell University Medical College, 1300 York Avenue, 10021, New York, NY, USA

    J. C. K. Lai & A. J. L. Cooper

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  1. J. C. K. Lai
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  4. E. Hertz
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Additional information

This paper is dedicated to Professor E. Kvamme. Dr. Kvamme has conducted numerous pioneering studies on the regulation of the metabolism of glutamine, glutamate and ammonia in nervous and other tissues (see Refs. 1 and 3 for a complete discussion and citation of his many papers). Many important ideas in this exciting field of research have emerged from the work carried out in his laboratory.

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Lai, J.C.K., Murthy, C.R.K., Cooper, A.J.L. et al. Differential effects of ammonia and β-methylene-dl-aspartate on metabolism of glutamate and related amino acids by astrocytes and neurons in primary culture. Neurochem Res 14, 377–389 (1989). https://doi.org/10.1007/BF01000042

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