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Effects of ammonia onl-glutamate uptake in cultured astrocytes

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Abstract

The effect of ammonia onl-glutamate (L-GLU) uptake was examined in cultured astrocytes. Acute ammonia treatment (5–10 mM) enhanced L-[3H]GLU uptake by 20–42% by increasing the Vmax; this persisted for 2 days and then started to decline. Ammonia, however, did not affect the uptake ofd-[3H]aspartate (D-ASP), a non-metabolizable analog of L-GLU, that uses the same transport carrier as L-GLU. Also, L-GLU uptake was not affected during the first 2 min of the assay. Thus, ammonia did not have an acute effect on L-GLU transport (translocation); rather, ammonia enhanced the accumulation or “trapping” of L-GLU or its by-products. Chronic ammonia treatment, on the other hand, inhibited L-GLU transport in astrocytes by ∼30–45% and this was due to a decrease in Vmax, suggesting that the number of L-GLU transporters was decreased. This inhibitory effect was observed after 1 day of treatment and persisted for at least 7 days. The inhibition of L-GLU transport was partially reversible following removal of ammonia. The effects of ammonia on L-GLU transport and uptake may explain the abnormal L-GLU neurotransmission observed in hyperammonemia/hepatic encephalopathy, and the brain swelling associated with fulminant hepatic failure.

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Authors and Affiliations

  1. Laboratory of Neuropathology, Veterans Administration Medical Center, University of Miami School of Medicine, P.O. Box 016960, 33101, Miami, FL, USA

    Alex S. Bender &  Michael D. Norenberg M.D.

  2. Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, P.O. Box 016960, 33101, Miami, FL, USA

    Michael D. Norenberg M.D.

  3. Department of Pathology (D-33), University of Miami School of Medicine, P.O. Box 016960, 33101, Miami, FL, USA

    Alex S. Bender &  Michael D. Norenberg M.D.

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Bender, A.S., Norenberg, M.D. Effects of ammonia onl-glutamate uptake in cultured astrocytes. Neurochem Res 21, 567–573 (1996). https://doi.org/10.1007/BF02527755

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