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Inhibition of mitochondrial respiration by 1,2,3,4-tetrahydroisoquinoline-like endogenous alkaloids in mouse brain

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Abstract

Since the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, it has been postulated that (a) MPTP-like toxin(s) such as 1,2,3,4-tetrahydroisoquinoline (TIQ) may induce Parkinson's disease. As the neuronal degeneration in MPTP-induced parkinsonism is thought to be caused by the inhibition of the mitochondrial respiration by 1-methyl-4-phenylpyridinium ion (MPP+), we studied the effects of TIQ-like alkaloids including dopaminederived ones on the mitochondrial respiration using mouse brains. TIQ, tetrahydropapaveroline (THP), and tetrahydropapaverine (THPV) produced significant inhibition of the state 3 and 4 respiration and respiratory control ratio supported by glutamate + malate, the activity of Complex 1 and the ATP synthesis. Among those compounds, THPV was most potent. Toxic properties of these compounds on mitochondria were quite similar to that of MPP+. Our results support the hypothesis that (a) MPTP- or MPP+-like substance(s) may be responsible for the nigral degeneration in Parkinson's disease.

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Abbreviations

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MPP+ :

1-methyl-4-phenylpyridinium ion

ATP:

adenosine triphosphate

ADP:

Adenosine diphosphate

TCL:

tricarboxylic acid

TIQ:

cycle: 1,2,3,4-Tetrahydroisoquinoline

THPV:

Tetrahydropapaverine

THP:

Tetrahydropaveroline

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Authors and Affiliations

  1. Department of Neurology, Jichi Medical School, 3311 Yakushiji, 329-04, Minamikawachi, Tochigi, Japan

    Keiji Suzuki & Mitsuo Yoshida

  2. Department of Neurology, Juntehdo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113, Tokyo, Japan

    Yoshikuni Mizuno

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  1. Keiji Suzuki
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Suzuki, K., Mizuno, Y. & Yoshida, M. Inhibition of mitochondrial respiration by 1,2,3,4-tetrahydroisoquinoline-like endogenous alkaloids in mouse brain. Neurochem Res 15, 705–710 (1990). https://doi.org/10.1007/BF00973651

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