The endogenous amine 1-methyl-1,2,3,4- tetrahydroisoquinoline prevents the inhibition of complex I of the respiratory chain produced by MPP(+).
The endogenous monoamine 1-methyl-1,2,3,4-tetrahydroisoquinoline has been shown to prevent the neurotoxic effect of MPP(+) and other endogenous neurotoxins, which produce a parkinsonian-like syndrome in humans. We have tested its potential protective effect in vivo by measuring the protection of 1-methyl-1,2,3,4-tetrahydroisoquinoline in the neurotoxicity elicited by MPP(+) in rat striatum by tyrosine hydroxylase immunocytochemistry. Because we know that cellular damage caused by MPP(+) is primarily the result of mitochondrial respiratory inhibition at the complex I level, we have extended the study further to understand this protective mechanism. We found that the inhibitory effect on the mitochondrial respiration rate induced by MPP(+) in isolated rat liver mitochondria and striatal synaptosomes was prevented by addition of 1-methyl-1,2,3,4-tetrahydroisoquinoline. This compound has no antioxidant capacity; therefore, this property is not involved in its protective effect. Thus, we postulate that the preventive effect that 1-methyl-1,2,3,4-tetrahydroisoquinoline has on mitochondrial inhibition for MPP(+) could be due to a "shielding effect," protecting the energetic machinery, thus preventing energetic failure. These results suggest that this endogenous amine may protect against the effect of several parkinsonism-inducing compounds that are associated with progressive impairment of the mitochondrial function.
Parrado
J
J
Departamento de Bioquimica, Bromatologia y Toxicologia, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
Absi
E
E
Ayala
A
A
Castaño
A
A
Cano
J
J
Machado
A
A
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000648:ultrastructure; D003342:Corpus Striatum / Q000187:drug effects / Q000648:ultrastructure; D042967:Electron Transport Complex I; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000648:ultrastructure; D044005:Tetrahydroisoquinolines; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D000975:Antioxidants; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C050386:1-methyl-1,2,3,4-tetrahydroisoquinoline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D015655:1-Methyl-4-phenylpyridinium