当前位置： SCI文献检索 > JOURNAL OF NEUROCHEMISTRY期刊下所有文献 > Potentiation by the tetraphenylboron anion of the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and its pyridinium metabolite.

Potentiation by the tetraphenylboron anion of the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and its pyridinium metabolite.

Abstract：

:The 1-methyl-4-phenylpyridinium species (MPP+) is the four-electron oxidation product of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and is widely assumed to be the actual neurotoxic species responsible for the MPTP-induced destruction of dopaminergic neurons. MPTP is oxidized by the enzyme monoamine oxidase-B to a dihydropyridinium intermediate which is oxidized further to MPP+, an effective inhibitor of the oxidation of the Complex I substrates glutamate/malate in isolated mitochondrial preparations. In the present study, the tetraphenylboron anion (TPB) greatly potentiated the inhibitory effects of MPP+ and other selected pyridinium species on glutamate/malate respiration in isolated mouse liver mitochondria. At 10 microM TPB, the potentiation ranged from approximately 50-fold to greater than 1,000-fold for the several pyridinium species tested. In other experiments, TPB greatly enhanced the accumulation of [3H]MPP+ by isolated mitochondrial preparations. This facilitation by TPB of MPP+ accumulation into mitochondria explains, at least in part, the potentiation by TPB of the above-mentioned inhibition of mitochondrial respiration. Moreover, TPB addition increased the amount of lactate formed during the incubation of mouse neostriatal tissue slices with MPTP and other tetrahydropyridines. The administration of TPB also potentiated the dopaminergic neurotoxicity of MPTP in male Swiss-Webster mice. All of these observations, taken together, are consistent with the premise that the inhibitory effect of MPP+ on mitochondrial respiration within dopaminergic neurons is the ultimate mechanism to explain MPTP-induced neurotoxicity.

journal_name

J Neurochem

journal_title

Journal of neurochemistry

authors

Heikkila RE,Hwang J,Ofori S,Geller HM,Nicklas WJ

doi

10.1111/j.1471-4159.1990.tb02314.x

subject

Has Abstract

pub_date

1990-03-01 00:00:00

pages

743-50

issue

3

eissn

0022-3042

issn

1471-4159

journal_volume

54

pub_type

杂志文章

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