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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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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DOI: https://doi.org/10.1007/BF00973651