Matsubara K, Senda T, Uezono T, Awaya T, Ogawa S, Chiba K, Shimizu K, Hayase N, Kimura K
Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical College, Asahikawa, 078-8510, Japan.
Neurosci Lett. 2001 Apr 20;302(2-3):65-8. doi: 10.1016/s0304-3940(01)01601-9.
N-Methyl-4-phenylpyridinium (MPP(+)) and 2,9-di-methyl-norharmanium (2,9-Me2NH(+)), which is a beta-carbolinium proposed as an endogenous MPP(+)-like toxin underlying Parkinson's disease, are strong mitochondrial toxins. We have measured the extracellular lactate levels as a marker for the in vivo cell hypoxia in the striatum of freely moving rats. The perfusions with MPP(+) and 2,9-Me2NH(+) increased extracellular lactate levels in a dose-dependent manner. These increases in lactate levels were significantly prevented by the co-perfusion with 10 microM L-deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, but not by pargyline, a non-specific MAO inhibitor. The increase in extracellular lactate levels was considered to be the reflection of the cell damage resulted from the impairment of mitochondrial function. The present results suggested that L-deprenyl would rescue nerve cells from these toxins through the direct influence on the mitochondrial electron transport.
N-甲基-4-苯基吡啶鎓（MPP(+)）和2,9-二甲基去甲哈尔满鎓（2,9-Me2NH(+)）是强效的线粒体毒素，2,9-Me2NH(+)是一种β-咔啉鎓，被认为是帕金森病潜在的内源性类MPP(+)毒素。我们测量了细胞外乳酸水平，以此作为自由活动大鼠纹状体体内细胞缺氧的标志物。用MPP(+)和2,9-Me2NH(+)灌注会使细胞外乳酸水平呈剂量依赖性增加。与10微摩尔左旋丙炔苯丙胺（一种选择性单胺氧化酶（MAO）-B抑制剂）共同灌注可显著阻止乳酸水平的这些升高，但非特异性MAO抑制剂帕吉林则无此作用。细胞外乳酸水平的升高被认为是线粒体功能受损导致细胞损伤的反映。目前的结果表明，左旋丙炔苯丙胺可通过对线粒体电子传递的直接影响，使神经细胞免受这些毒素的侵害。
