Inhibitory Effects of Endogenous Tetrahydroisoquinolines on Mitochondrial Respiration in Mouse Brain
Pathogenesis of Parkinson’s disease has not been well elucidated yet. However, some hypotheses have been advocated. Mitochondrial abnormalities,1,2,3,4,5,6 and changes of iron and free radicals7,8 have been reported. The mechanism of nigrostriatal degeneration in MPTP-induced parkinsonism appears to be due to the inhibition of mitochondrial respiration by MPP+. 9,10,11,12 Chronic exposure to an unknown MPTP-like endogenous neurotoxin has been postulated as a possible etiology of Parkinson’s disease. 1,2,3,4-Tetrahydroisoquinoline (TIQ) has emerged as one of such toxins.13 We have previously reported the effects of TIQ14,15,16,17 and TIQ-related compounds18 on mitochondrial respiration. In the present study, we report the inhibitory effect of dopamine-derived endogenous tetrahydroisoquinolines against mitochondrial respiration.
KeywordsTyrosine Hydroxylase Mouse Brain Mitochondrial Respiration Inhibitory Potency Electron Transport System
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- 8.D.T. Dexter, A. Carayon, F. Javoy-Agid, Y. Agid, F. R. Wells, S.E. Daniel, A.J. Lees, P. Jenner and C.D. Marsden, Alterations in the levels of iron, ferritin and other trace metals in Parkinson’s disease and other neurodegenerative diseases affecting the basal ganglia, Brain 114: 1953 (1991).PubMedCrossRefGoogle Scholar
- 17.K. Suzuki, Y. Mizuno and M. Yoshida, Effects of tetrahydroisoquinoline on mitochondrial respiration, in: “Basic, Clinical, and Therapeutic Aspects of Alzheimer’s and Parkinson’s Diseases”, T. Nagatsu et al. ed., Plenum Press, New York Vol. 1, p. 309, (1990).Google Scholar
- 20.S. Ohta, M. Kohno, Y. Makino, O. Tachikawa and M. Hirobe, Tetrahydroisoquinoline and 1-methyltetrahydroisoquinoline are present in the human brain: relation to Parkinson’s disease, Biomed. Res. 8: 453 (1987).Google Scholar
- 26.P. Dostert, M.S. Benedetti and G. Dordain, Tetrahydroisoquinoline alkaloids in neurodegenerative disorders - influence of drug treatment, in: “Basic, Clinical, and Therapeutic Aspects of Alzheimer’s and Parkinson’s Diseases”, Vol. 1, p. 247, T. Nagatsu et al. ed., Plenum Press, New York (1990).Google Scholar
- 27.W. Maruyama, D. Nakahara, M. Ota, T. Takahashi, A. Takahashi, T. Nagatsu and M. Naoi, Nmethylation of dopamine-derived 6,7-dihydroxy-1,2,3,4-tetrahydroiso-quinoline, (R)-salsolinol, in rat brains: in vivo microdialysis study, J. Neurochem. 59:395 (1992).Google Scholar
- 28.T. Niwa, N. Takeda, H. Yoshizumi, A. Tatematsu, M. Yoshida, P. Dostert, M. Naoi and T. Nagatsu, Presence of 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolineand 1,2-dimethyl-6,7dihydroxy-1,2,3,4-tetrahydroisoquinoline, novel endogenous amines, in parkinsonian and normal human brains, Biochem. Biophys. Res. Commun. 177: 603 (1991).PubMedCrossRefGoogle Scholar