Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-like compounds on mitochondrial respiration.
Effects of MPTP-like compounds on mitochondrial respiration, activity of NADH-ubiquinone oxidoreductase (complex I) and on ATP synthesis were reported. Mitochondria prepared from mouse whole brains were used. The compounds tested include tetrahydroisoquinoline (TIQ), tetrahydropapaveroline (THP), tetrahydropapaverine (THPV), and salsolinol. TIQ, THP, and THPV significantly inhibited the state 3 respiration supported by glutamate + malate, activity of complex I and ATP synthesis. Among these compounds, THPV was most potent. Toxic properties of these compounds on mitochondria were similar to MPP+. Significance of our results was discussed with respect to etiology of Parkinson's disease.
Suzuki
K
K
Department of Neurology, Jichi Medical School, Tochigi, Japan.
Mizuno
Y
Y
Yoshida
M
M
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects*; D016660:NAD(P)H Dehydrogenase (Quinone); D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D011808:Quinone Reductases / Q000037:antagonists & inhibitors; D044005:Tetrahydroisoquinolines; D013765:Tetrahydropapaveroline / Q000494:pharmacology
D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C063395:tetrahydropapaverine; D013765:Tetrahydropapaveroline; C014843:1,2,3,4-tetrahydroisoquinoline; D000255:Adenosine Triphosphate; C036617:salsolinol; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases