Cyperquat (MPP+), but not MPTP or Paraquat Inhibits Oxygen Consumption in Mitochondria from Rat Striatum
l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) is known to induce parkinsonism in man and in several laboratory animal species1–4. MPTP binds to monoamine oxidase (MAO) sites in most brain areas, including the substantia nigra and striatum5. MAO oxidises MPTP to l-methyl-4-phenyl pyridinium ion (MPP+) which induces neurotoxicity by a mechanism(s) not yet elucidated. Pretreatment of animals with MAO-B inhibitors, for example, pargyline, prevents MPTP-induced parkinsonism6,7. In contrast, MAO-A inhibitors, such as clorgyline, is not effective in preventing MPTP-induced toxicity6,8.
KeywordsOxygen Consumption Rate Flavin Adenine Dinucleotide Flavin Adenine Dinucleotide Mitochondrial Preparation Phenyl Pyridinium
Unable to display preview. Download preview PDF.
- 2.R.S. Burns, C.C. Chiueh, S.P. Markey, M.H. Ebert, D.M. Jacobowitz, and I.J. Kopin, “A Primate Model of Parkinsonism: Selective Destruction of Dopaminergic Neurons in the Pars Compacta of the Substantia Nigra by N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine”. Proc. Natl. Acad. Sci. U.S.A., 80:4546 (1983).PubMedCrossRefGoogle Scholar
- 9.J.H. Thakar, M.N. Hassan, and J.D. Grimes, “In vitro Effects of Dopamine Active Compounds on Mitochondrial Respiration and Oxidative Phosphorylation From Rat Cortex, Striatum and Liver. 15th Annual Meeting, Society for Neuroscience, Abstract #350.4 (1985).Google Scholar
- 10.D. Cavalla, M. Hadjiconstantinou, H.E. Laird II, and N.H. Neff, “Intracerebroventricular Administration of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its Metabolite l-methyl-4-phenylpyridinium Ion (MPP+) Decrease Dopamine and Increase Acetylcholine in the Mouse Neostriatum”. Neuropharmacol., 24:585 (1985).CrossRefGoogle Scholar
- 15.J.H. Thakar, M.N. Hassan, and J.D. Grimes, “In Vitro Effects of MPTP and Related Compounds Paraquat and Cyperquat (MPP+) on Oxidative Phosphorylation of Mitochondria from Rat Cortex, Striatum and Liver”. 16th Annual Meeting, Society for Neuroscience, Abstract #28.7 (1986).Google Scholar