Anderzhanova Elmira, Oja Simo S, Saransaari Pirjo, Albrecht Jan
Brain Research Center, University of Tampere Medical School, Tampere, Finland.
Brain Res. 2003 Jul 11;977(2):290-3. doi: 10.1016/s0006-8993(03)02777-x.
Acute hyperammonemia is associated with motor disturbances that are thought to involve striatal dopaminergic dysfunction. Discharge of striatal dopaminergic neurons is controlled by N-methyl-D-aspartate (NMDA) receptors, the excessive activation of which contributes to ammonia neurotoxicity. Here we show that ammonium chloride ("ammonia", extracellular concentration 5 mM) or NMDA (1 mM), when directly administered to the rat striatum via a microdialysis probe, evoke a prompt accumulation of dopamine (DA) in the microdialysates. However, while ammonia increases, NMDA decreases, the extracellular dihydroxyphenylacetate (DOPAC) level. The results point to the NMDA receptor-mediated enhancement of DA release and increased DA metabolism as two independent ways by which ammonia affects the striatal dopaminergic system. Taurine (extracellular concentration 10 mM) attenuated the NMDA- and ammonia-evoked DA release and ammonia-induced accumulation of DOPAC, reflecting two different neuroprotective mechanisms of this amino acid.
急性高氨血症与运动障碍有关，人们认为运动障碍涉及纹状体多巴胺能功能障碍。纹状体多巴胺能神经元的放电受N-甲基-D-天冬氨酸（NMDA）受体控制，该受体的过度激活会导致氨神经毒性。我们在此表明，当通过微透析探针直接将氯化铵（“氨”，细胞外浓度5 mM）或NMDA（1 mM）注入大鼠纹状体时，会促使微透析液中多巴胺（DA）迅速积累。然而，虽然氨会增加，但NMDA会降低细胞外二羟基苯乙酸（DOPAC）水平。结果表明，NMDA受体介导的DA释放增强和DA代谢增加是氨影响纹状体多巴胺能系统的两种独立方式。牛磺酸（细胞外浓度10 mM）减弱了NMDA和氨诱发的DA释放以及氨诱导的DOPAC积累，这反映了这种氨基酸的两种不同神经保护机制。
