Neurotoxicity Research

, Volume 4, Issue 2, pp 127–131

Inhibition of DT-diaphorase is a requirement for Mn3+ to produce a 6-OH-dopamine like rotational behaviour

  • J. Segura-aguilar
  • G. Diaz-Veliz
  • S. Mora
  • M. Herrera-Marschitz
Article

Abstract

Intracerebral managanese administration together with the DT-diaphorase inhibitor dicoumarol (Mn3+ 40 nmol+-dicoumarol 2 nmol; in 4 μl) into the left medial forebrain bundle (MFB) produced a behavioural pattern characterised by contralateral behaviour when the rats were stimulated with apomorphine (0.5 mg/kg s.c.), in a manner similar to that when administered to unilaterally 6-hydroxy-dopamine-lesioned animals. The same animals rotated towards the opposite side (ipsilaterally) when stimulated with d-amphetamine (2 mg/kg s.c.). These results support the idea that DT-diaphorase plays a protective role in the dopaminergic systems.

Keywords

Aminochrome Dicoumarol Dopamine 6-OH-dopamine DT-diaphorase Manganese 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Baez, S., Linderson, Y. and Segura-Aguilar, J. (1995) “Superoxide dismutase and catalase enhance autoxidation during one-electron reduction of aminochrome by NADPH-cytochrome P-450 reductase”, Biochem. Mol. Med. 54, 12–18.PubMedCrossRefGoogle Scholar
  2. Herrera-Marschitz, M. and Ungersted, U. (1984a) “Evidence that apomorphine and pergolide induce rotation in rats by different actions on D1 and D2 receptors sites”, Eur. J. Pharmacol. 98, 165–176.PubMedCrossRefGoogle Scholar
  3. Herrera-Marschitz, M. and Ungersted, U. (1984b) “Evidence that striatal afferents related to different dopamine receptors”, Brain Res. 323, 269–278.PubMedCrossRefGoogle Scholar
  4. Kilpatrick, I.C., Starr, M.S., Fletcher, A., James, T.A. and MacLeod, N.K. (1980) “Evidence for a GaBAergic nigrotectal amino butyrate-containing neurons in striatal and nigral-derived circlingin the rat”, Neuroscience, 7, 207–222.CrossRefGoogle Scholar
  5. Langston, J.W. and Ballard, Jr., P.A. (1983) “Parkinson’s disease in a chemist working with 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine”, N. Engl. J. Med. 309, 310.PubMedGoogle Scholar
  6. Naoi, M., Maruyama, W., Dostert, P., Hashizume, Y., Nakahara, D., Takahashi, T. and Ota, M. (1996) “Dopamine-derived endogenous 1 (R), 2 (N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, N-methyl-(R)-salsolinol, induced parkinsonism in rat: biochemical, pathological and behavioral studies”, Brain Res. 709, 285–295.PubMedCrossRefGoogle Scholar
  7. Paris, I., Dagnino-Subiabre, A., Marcelain, K., Bennett, L.B., Caviedes, P., Caviedes, R., Olea Azar, C. and Segura-Aguilar, J. (2001) “Copper neurotoxicity is dependent on dopaminemediated copper uptake and one-electron reduction of aminochrome in rat substantia nigra neuronal cell line”, J. Neurochem. 77, 519–529.PubMedCrossRefGoogle Scholar
  8. Segura-Aguilar, J., and Lind, C. (1989) “On the mechanism of Mn3+ induce neurotoxicity of dopamine: prevention of quinone derived oxygen toxicity by DT-diaphorase and superoxid dismutase”, Chem. Biol. Interact. 72, 309–324.PubMedCrossRefGoogle Scholar
  9. Segura-Aguilar, J., Metodiewa, D. and Welch, C.J. (1998) “Metabolic activation of dopamine o-quinones to o-semi quinones by NADPH cytochrome P450 reductase may play an important role in oxidative stress and apoptotic effects”, Biochim. Biophys. Acta 1381, 1–6.PubMedGoogle Scholar
  10. Schultzberg, M., Segura-Aguilar, J. and Lind, C. (1988) “Distribution of DT-diaphorase in the rat brain: biochemical and immunohistochemical studies”, Neuroscience 27, 763–766.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2002

Authors and Affiliations

  • J. Segura-aguilar
    • 1
  • G. Diaz-Veliz
    • 1
  • S. Mora
    • 1
  • M. Herrera-Marschitz
    • 1
    • 2
  1. 1.Faculty of Medicine, Program of Molecular and Clinical Pharmacology, ICBMUniversity of ChileSantiago-7Chile
  2. 2.Department of Physiology and PharmacologyKarolinska InstitutetStockholmSweden

Personalised recommendations