Effects of ammonia on L-glutamate uptake in cultured astrocytes.
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 Vmax; this persisted for 2 days and than 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 min of the assay. Thus, ammonia did not have an acute effect of 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 approximately 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.
Bender
A S
AS
Laboratory of Neuropathology, Veterans Administration Medical Center, Miami, FL, USA.
Norenberg
M D
MD
D000641:Ammonia / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism*; D007700:Kinetics; D051381:Rats
D001224:Aspartic Acid; D018698:Glutamic Acid; D000641:Ammonia