Bender A S, Norenberg M D
Laboratory of Neuropathology, Veterans Administration Medical Center, Miami, FL, USA.
Neurochem Res. 1996 May;21(5):567-73. doi: 10.1007/BF02527755.
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.
在培养的星形胶质细胞中检测了氨对L-谷氨酸（L-GLU）摄取的影响。急性氨处理（5-10 mM）通过增加Vmax使L-[3H]GLU摄取提高了20-42%；这种情况持续2天，然后开始下降。然而，氨并不影响L-GLU的非代谢类似物D-[3H]天冬氨酸（D-ASP）的摄取，D-ASP与L-GLU使用相同的转运载体。此外，在测定的前2分钟内L-GLU摄取不受影响。因此，氨对L-GLU转运（易位）没有急性作用；相反，氨增强了L-GLU或其副产物的积累或“捕获”。另一方面，慢性氨处理使星形胶质细胞中的L-GLU转运受到约30-45%的抑制，这是由于Vmax降低，表明L-GLU转运体数量减少。这种抑制作用在处理1天后即可观察到，并持续至少7天。去除氨后，L-GLU转运的抑制作用部分可逆。氨对L-GLU转运和摄取的影响可能解释了高氨血症/肝性脑病中观察到的异常L-GLU神经传递，以及与暴发性肝衰竭相关的脑肿胀。
