Effects of ammonia on L-glutamate uptake in cultured astrocytes

Alex S. Bender, Michael D. Norenberg

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


The effect of ammonia on L-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 V(max); this persisted for 2 days and then started to decline. Ammonia, however, did not affect the uptake of D- [ 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 thin 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 V(max), 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.

Original languageEnglish (US)
Pages (from-to)567-573
Number of pages7
JournalNeurochemical Research
Issue number5
StatePublished - May 1996


  • Ammonia
  • astrocytes
  • cell swelling
  • glutamate uptake
  • glutamine
  • hepatic encephalopathy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry


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