Matsubara K, Idzu T, Kobayashi Y, Nakahara D, Maruyama W, Kobayashi S, Kimura K, Naoi M
Department of Legal Medicine, Shimane Medical University, Izumo, Japan.
Neurosci Lett. 1995 Oct 27;199(3):199-202. doi: 10.1016/0304-3940(95)12050-e.
The effects of N-methyl-4-phenylpyridinium (MPP+) and its endogenous analog, 2,9-di-methyl-norharmanium (2,9-Me2NH+), on in vivo tyrosine hydroxylation were evaluated in freely moving rats. MPP+ gradually but almost completely reduced tyrosine hydroxylation, even at a dose as low as 0.05 mM. This effect was considered to be caused by the inhibition of tyrosine hydroxylase (TH) activation. On the contrary, 1 mM 2,9-Me2NH+ rapidly reduced 3,4-dihydroxyphenylalanine production to 10% of the basal level only during its perfusion, indicating direct inhibition of TH activity. The present study revealed that MPP+ and 2,9-Me2NH+ were taken up into dopaminergic neurons and then inhibited in vivo dopamine synthesis prior to cell death possibly in different manners.
在自由活动的大鼠中评估了N-甲基-4-苯基吡啶鎓（MPP+）及其内源性类似物2,9-二甲基去氢骆驼蓬碱（2,9-Me2NH+）对体内酪氨酸羟化作用的影响。即使在低至0.05 mM的剂量下，MPP+也会逐渐但几乎完全降低酪氨酸羟化作用。这种效应被认为是由酪氨酸羟化酶（TH）激活的抑制所引起的。相反，仅在灌注期间，1 mM的2,9-Me2NH+迅速将3,4-二羟基苯丙氨酸的产生降低至基础水平的10%，表明对TH活性有直接抑制作用。本研究表明，MPP+和2,9-Me2NH+被摄取到多巴胺能神经元中，然后在细胞死亡之前可能以不同方式抑制体内多巴胺合成。
