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N-甲基-4-苯基吡啶（MMP+）与6-羟基多巴胺或多巴胺一起刺激线粒体释放钙离子。

N-methyl-4-phenylpyridine (MMP+) together with 6-hydroxydopamine or dopamine stimulates Ca2+ release from mitochondria.

作者信息

Frei B, Richter C

出版信息

FEBS Lett. 1986 Mar 17;198(1):99-102. doi: 10.1016/0014-5793(86)81192-9.

DOI:10.1016/0014-5793(86)81192-9
PMID:3082673
Abstract

The nigrostriatal neurotoxin N-methyl-1,2,3,6-tetrahydropyridine (MPTP) causes Parkinsonism in humans and laboratory animals. MPTP neurotoxicity is dependent on its oxidation to N-methyl-4-phenylpyridine (MPP+). The mechanism by which MPP+ causes destruction of dopamine-containing nigrostriatal cells is unknown. Here we show that MPP+ but not MPTP is taken up by energized mitochondria. MPP+ in the presence of dopamine and particularly of 6-hydroxydopamine stimulates Ca2+ release from mitochondria. Ca2+ release is accompanied by hydrolysis of intramitochondrial pyridine nucleotides. Our findings suggest that the MPTP-induced model of Parkinson's disease may be due to a disturbed Ca2+ homeostasis in dopamine neurons.

摘要

黑质纹状体神经毒素N-甲基-1,2,3,6-四氢吡啶（MPTP）可导致人类和实验动物患帕金森症。MPTP的神经毒性取决于其氧化为N-甲基-4-苯基吡啶（MPP+）。MPP+导致含多巴胺的黑质纹状体细胞破坏的机制尚不清楚。在此我们表明，有活性的线粒体摄取的是MPP+而非MPTP。在多巴胺尤其是6-羟基多巴胺存在的情况下，MPP+会刺激线粒体释放Ca2+。Ca2+的释放伴随着线粒体内吡啶核苷酸的水解。我们的研究结果表明，MPTP诱导的帕金森病模型可能是由于多巴胺能神经元中Ca2+稳态受到干扰所致。

相似文献

1
N-methyl-4-phenylpyridine (MMP+) together with 6-hydroxydopamine or dopamine stimulates Ca2+ release from mitochondria.N-甲基-4-苯基吡啶（MMP+）与6-羟基多巴胺或多巴胺一起刺激线粒体释放钙离子。
FEBS Lett. 1986 Mar 17;198(1):99-102. doi: 10.1016/0014-5793(86)81192-9.
2
Dopamine-releasing action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP+) in the neostriatum of the rat as demonstrated in vivo by the push-pull perfusion technique: dependence on sodium but not calcium ions.用推挽灌注技术在大鼠体内证实1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）和1-甲基-4-苯基吡啶（MPP+）在新纹状体中的多巴胺释放作用：依赖钠离子而非钙离子。
Brain Res. 1988 Mar 8;443(1-2):101-16. doi: 10.1016/0006-8993(88)91603-4.
3
Histochemistry of MPTP oxidation in the rat brain: sites of synthesis of the parkinsonism-inducing toxin MPP+.
Neurosci Lett. 1986 Apr 24;65(3):321-5. doi: 10.1016/0304-3940(86)90282-x.
4
1-methyl-4-phenylpyridine is neurotoxic to the nigrostriatal dopamine pathway.1-甲基-4-苯基吡啶对黑质纹状体多巴胺能通路具有神经毒性。
Nature. 1986;319(6048):56-7. doi: 10.1038/319056a0.
5
MPTP: an industrial chemical and contaminant of illicit narcotics stimulates a new era in research on Parkinson's disease.1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）：一种工业化学品及非法麻醉品污染物开启了帕金森病研究的新时代。
Environ Health Perspect. 1987 Nov;75:45-51. doi: 10.1289/ehp.877545.
6
Dopaminergic toxicity of rotenone and the 1-methyl-4-phenylpyridinium ion after their stereotaxic administration to rats: implication for the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity.鱼藤酮和1-甲基-4-苯基吡啶离子立体定位注射给大鼠后的多巴胺能毒性：对1-甲基-4-苯基-1,2,3,6-四氢吡啶毒性机制的启示
Neurosci Lett. 1985 Dec 18;62(3):389-94. doi: 10.1016/0304-3940(85)90580-4.
7
Mechanism of the neurotoxicity of 1-methyl-4-phenylpyridinium (MPP+), the toxic bioactivation product of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).1-甲基-4-苯基吡啶鎓（MPP+）的神经毒性机制，1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的有毒生物活化产物。
Toxicology. 1988 Apr;49(1):17-23. doi: 10.1016/0300-483x(88)90169-2.
8
Energy-driven uptake of N-methyl-4-phenylpyridine by brain mitochondria mediates the neurotoxicity of MPTP.脑线粒体对N-甲基-4-苯基吡啶的能量驱动摄取介导了MPTP的神经毒性。
Life Sci. 1986 Aug 18;39(7):581-8. doi: 10.1016/0024-3205(86)90037-8.
9
Studies on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: inhibition of NAD-linked substrate oxidation by its metabolite, 1-methyl-4-phenylpyridinium.1-甲基-4-苯基-1,2,3,6-四氢吡啶的神经毒性研究：其代谢产物1-甲基-4-苯基吡啶鎓对烟酰胺腺嘌呤二核苷酸（NAD）相关底物氧化的抑制作用
J Neurochem. 1986 May;46(5):1501-7. doi: 10.1111/j.1471-4159.1986.tb01768.x.
10
4-Phenylpyridine (4PP) and MPTP: the relationship between striatal MPP+ concentrations and neurotoxicity.4-苯基吡啶（4PP）与1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）：纹状体中1-甲基-4-苯基吡啶离子（MPP+）浓度与神经毒性之间的关系。
Life Sci. 1987 Feb 23;40(8):731-40. doi: 10.1016/0024-3205(87)90300-6.

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