Skip to main content
SpringerLink
Log in

6-Hydroxydopa, a Catecholamine Neurotoxin and Endogenous Excitotoxin at Non-NMDA Receptors

  • Chapter
Highly Selective Neurotoxins

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

By the late 1960s, 6-hydroxydopamine (6-OHDA) was recognized as a substance that would produce long-lasting depletion of norepinephrine (NE) from the heart and other organs (1–3), by virtue of overt destruction of sympathetic innervation to these tissues (4, 5). However, systemically administered 6-OHDA was restricted to noncentral compartments by the blood—brain barrier. 6-Hydroxydopa (6-OHDOPA) was synthesized specifically to overcome this limitation. Being an amino acid, 6-OHDOPA would be transported by facilitated diffusion into the brain, where abundant decarboxylase enzymes could convert this metabolic precursor to the active neurotoxic species, 6-OHDA, which then could produce damage to catecholamine- (CA) containing neurons in brain (Fig. 1).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. Porter, C. C., Totaro, J. A., and Stone, C. A. (1963) Effect of 6-hydroxydopamine and some other compounds on the concentration of norepinephrine in the hearts of mice. J. Pharmacol. Exp. Ther. 140, 308–316.

    PubMed  CAS  Google Scholar 

  2. Porter, C. C., Totaro, J. A., and Burcin, A. (1965) The relationship between radioactivity and norepinephrine concentrations in the brains and hearts of mice following administration of labelled methyldopa or 6-hydroxydopamine. J. Pharmacol. Exp. Ther. 150, 17–22.

    PubMed  CAS  Google Scholar 

  3. Stone, C. A., Stavorski, J. M., Ludden, C. T., Wengler, H. C., Ross, C. A., Totaro, J. A., and Porter, C. C. (1963) Comparison of some pharmacological effects of certain 6-substituted dopamine derivatives with reserpine, guanethidine and metaraminol. J. Pharmacol. Exp. Ther. 142, 147–156.

    PubMed  CAS  Google Scholar 

  4. Tranzer, J. P. and Thoenen, H. (1967) Ultra-morphologische Veranderungen der sympa-tischen Nervendigunden der Katze nach Vorbehandlung mit 5- und 6-hydroxy-dopamin. Naunyn-Schmiedebergs Arch. Pharmakol. Exp. Pathol. 257, 343–344.

    Google Scholar 

  5. Thoenen, H. and Tranzer, J. P. (1968) Chemical sympathectomy by selective destruction of adrenergic nerve endings with 6-hydroxydopamine. Naunyn-Schmiedebergs Arch. Pharmakol. Exp. Pathol. 261, 271–288.

    CAS  Google Scholar 

  6. Ong, H. H., Creveling, C. R., and Daly, J. W. (1969) The synthesis of 2,4,5-trihydroxyphenylalanine (6-hydroxydopa). A centrally active norepinephrine-depleting agent. J. Med. Chem. 12, 458–462.

    PubMed  CAS  Google Scholar 

  7. Berkowitz, B. A., Spector, S., Brossi, A., Focella, A., and Teitel, S. (1970) Preparation and biological properties of (-)- and (+)-6-hydroxydopa. Experientia 26, 982–983.

    PubMed  CAS  Google Scholar 

  8. Olney, J. W., Zorumski, C. F., Stewart, G. R., Price, M. T., Wang, G.J., and Labruyere, J. (1990) Excitotoxicity of L-dopa and 6-OH-dopa: implications for Parkinson’s and Huntington’s diseases. Exp. Neurol. 108, 269–272.

    PubMed  CAS  Google Scholar 

  9. Janes, S. M., Mu, D., Wemmer, D., Smith, A. J., Kaur, S., Maltby, D., and Burlingame, A. L. (1990) A new redox cofactor in eukaryotic enzymes: 6-Hydroxydopa at the active site of bovine serum amine oxidase. Science 248, 981–987.

    PubMed  CAS  Google Scholar 

  10. Kostrzewa, R. M. and Jacobowitz, D. M. (1974) Pharmacological actions of 6-hydroxydopamine. Pharmacol. Rev. 26, 199–288.

    PubMed  CAS  Google Scholar 

  11. Kostrzewa, R. M. (1988) Reorganization of noradrenergic neuronal systems following neonatal chemical and surgical injury. Prog. Brain Res. 78, 405–423.

    Google Scholar 

  12. Kostrzewa, R. M. (1989) Neurotoxins that affect central and peripheral catecholamine neurons, in Neuromethods, vol. 12: Drugs as Tools in Neurotransmitter Research ( Boulton, A. A., Baker, G. B., and Juorio, A. V., eds.), Humana, Clifton, NJ, pp. 1–48.

    Google Scholar 

  13. Jacobowitz, D. and Kostrzewa, R. (1971) Selective action of 6-hydroxydopa on noradrenergic terminals: Mapping of preterminal axons of the brain. Life Sci. 10, 1329–1341.

    CAS  Google Scholar 

  14. Kostrzewa, R. and Jacobowitz, D. (1973) Acute effects of 6-hydroxydopa on central monoaminergic neurons. Eur. J. Pharmacol. 21, 70–80.

    PubMed  CAS  Google Scholar 

  15. Sachs, C. and Jonsson, G. (1972) Degeneration of central and peripheral noradrenaline neurons produced by 6-hydroxy-DOPA. J. Neurochem. 19, 1561–1575.

    PubMed  CAS  Google Scholar 

  16. Sachs, C. and Jonsson, G. (1972) Selective 6-hydroxy-DOPA induced degeneration of central and peripheral noradrenaline neurons. Brain Res. 40, 563–568.

    PubMed  CAS  Google Scholar 

  17. Richardson, J. S. and Jacobowitz, D. M. (1973) Depletion of brain norepinephrine by intraventricular injection of 6-hydroxydopa: A biochemical, histochemical and behavioral study in rats. Brain Res. 58, 117–133.

    PubMed  CAS  Google Scholar 

  18. Falck, B., Hillarp, N.-A., Thieme, G., and Torp, A. (1962) Fluorescence of catecholamines and related compounds condensed with formaldehyde. J. Histochem. Cytochem. 10, 348–354.

    CAS  Google Scholar 

  19. Cheah, T. B., Geffen, L. B., Jarrott, B., and Ostberg, A. (1971) Action of 6-hydroxydopamine on lamb sympathetic ganglia, vas deferens and adrenal medulla: A combined histochemical, ultrastructural and biochemical comparison with the effects of reserpine. Br. J. Pharmacol. 42, 543–557.

    PubMed  CAS  Google Scholar 

  20. Ross, R. A., Joh, T. H., and Reis, D. J. (1975) Reversible changes in the accumulation and activities of tyrosine hydroxylase and dopamine-13-hydroxylase in neurons of nucleus locus coeruleus during the retrograde reaction. Brain Res. 92, 57–72.

    PubMed  CAS  Google Scholar 

  21. Corrodi, H., Clark, W. G., and Masuoka, D. I. (1971) The synthesis and effects of DL-6hydroxydopa, in 6-Hydroxydopamine and Catecholamine Neurons (Malmfors, T. and Thoenen, H., eds.), North Holland, Amsterdam, pp. 187–192.

    Google Scholar 

  22. Clarke, D. E., Smookler, H. H., Hadinata, J., Chi, C., and Barry, H. III (1972) Acute effects of 6-hydroxydopa and its interaction with DOPA on brain amine levels. Life Sci. 11, 97–102.

    CAS  Google Scholar 

  23. Sachs, C., Jonsson, G., and Fuxe, K. (1973) Mapping of central noradrenaline pathways with 6-hydroxy-dopa. Brain Res. 63, 249–261.

    PubMed  CAS  Google Scholar 

  24. Tohyama, M., Maeda, T., and Shimizu, N. (1974) Detailed noradrenaline pathways of locus coeruleus neuron to the cerebral cortex with use of 6-hydroxydopa. Brain Res. 79, 139–144.

    CAS  Google Scholar 

  25. Lenard, L. and Hahn, Z. (1982) Amygdalar noradrenergic and dopaminergic mechanisms in the regulation of hunger and thirst-motivated behavior. Brain Res. 233, 115–132.

    PubMed  CAS  Google Scholar 

  26. Thoenen, H. (1972) Chemical sympathectomy: a new tool in the investigation of the physiology and pharmacology of peripheral and central adrenergic neurons, in Perspectives in Neuropharmacology (Snyder, S. H., ed.), Oxford University Press, London, pp. 302–338.

    Google Scholar 

  27. Kostrzewa, R. M. and Harper, J. W. (1974) Effects of 6-hydroxydopa on catecholaminecontaining neurons in brains of newborn rats. Brain Res. 69, 174–181.

    PubMed  CAS  Google Scholar 

  28. Kostrzewa, R. M. and Harper, J. W. (1975) Comparison of the neonatal effects of 6-hydroxydopa and 6-hydroxydopamine on growth and development of noradrenergic neurons in the central nervous system, in Chemical Tools in Catecholamine Research, vol. I, (Jonsson, G., Malmfors, T. and Sachs, C., eds.), North Holland, Amsterdam, pp. 181–188.

    Google Scholar 

  29. Clark, M. B., King, J. C., and Kostrzewa, R. M. (1979) Loss of nerve cell bodies in caudal locus coeruleus following treatment of neonates with 6-hydroxydopa. Neurosci. Lett. 13, 331–336.

    PubMed  CAS  Google Scholar 

  30. Kostrzewa, R. M., Klara, J. W., Robertson, J., and Walker, L. C. (1978) Studies on the mechanism of sprouting of noradrenergic terminals in rat and mouse cerebellum after neonatal 6-hydroxydopa. Brain Res. Bull. 3, 525–531.

    CAS  Google Scholar 

  31. Kostrzewa, R. and Jacobowitz, D. (1972) The effect of 6-hydroxydopa on peripheral adrenergic neurons. J. Pharmacol. Exp. Ther. 183, 284–297.

    PubMed  CAS  Google Scholar 

  32. Zieher, L. M. and Jaim-Etcheverry, G. (1973) Regional differences in the long-term effect of neonatal 6-hydroxydopa treatment on rat brain noradrenaline. Brain Res. 60, 199–207.

    PubMed  CAS  Google Scholar 

  33. Jaim-Etcheverry, G. and Zieher, L. M. (1975) Alterations of the development of central adrenergic neurons produced by 6-hydroxydopa, in Chemical Tools in Catecholamine Research, vol. I, (Jonsson, G., Malmfors, T. and Sachs, C., eds.), North Holland, Amsterdam, pp. 173–180.

    Google Scholar 

  34. Zieher, L. M. and Jaim-Etcheverry, G. (1975) Different alterations in the development of the noradrenergic innervation of the cerebellum and the brain stem produced by neonatal 6-hydroxydopa. Life. Sci. 17, 987–991.

    PubMed  CAS  Google Scholar 

  35. Zieher, L. M. and Jaim-Etcheverry, G. (1975) 6-Hydroxydopa during development of central adrenergic neurons produces different long-term changes in rat brain noradrenaline. Brain Res. 86, 271–281.

    Google Scholar 

  36. Kostrzewa, R. M. (1975) Effects of neonatal 6-hydroxydopa treatment on monamine content of rat brain and peripheral tissues. Res. Commun. Chem. Pathol. Pharmacol. 11, 567–579.

    PubMed  CAS  Google Scholar 

  37. Kostrzewa, R. M. and Garey, R. E. (1976) Effects of 6-hydroxydopa on noradrenergic neurons in developing rat brain. J. Pharmacol. Exp. Ther. 197, 105–118.

    PubMed  CAS  Google Scholar 

  38. Kostrzewa, R. M. and Garey, R. E. (1977) Sprouting of noradrenergic terminals in rat cerebellum following neonatal treatment with 6-hydroxydopa. Brain Res. 124, 385–391.

    PubMed  CAS  Google Scholar 

  39. Jaim-Etcheverry, G. and Zieher, L. M. (1977) Differential effect of various 6-hydroxydopa treatments on the development of central and peripheral noradrenergic neurons. Eur. J. Pharmacol. 45, 105–116.

    PubMed  CAS  Google Scholar 

  40. Harston, C. T., Morrow, A., and Kostrzewa, R. M. (1980) Enhancement of sprouting and putative regeneration of central noradrenergic fibers by morphine. Brain Res. Bull. 5, 421–424.

    PubMed  CAS  Google Scholar 

  41. Harston, C. T., Clark, M. B., Hardin, J. C., and Kostrzewa, R. M. (1981) Opiate-enhanced toxicity and noradrenergic sprouting in rats treated with 6-hydroxydopa. Eur. J. Pharmacol. 71, 365–373.

    PubMed  CAS  Google Scholar 

  42. Harston, C. T., Clark, M. B., Hardin, J. C., and Kostrzewa, R. M. (1982) Developmental localization of noradrenergic innervation to the rat cerebellum following neonatal 6-hydroxydopa and morphine treatment. Dey. Neurosci. 5, 252–262.

    CAS  Google Scholar 

  43. Kostrzewa, R. M., Harston, C. T., Fukushima, H., and Brus, R. (1982) Noradrenergic fiber sprouting in the cerebellum. Brain Res. Bull. 9, 509–517.

    PubMed  CAS  Google Scholar 

  44. Klisans-Fuenmayor, D., Harston, C. T., and Kostrzewa, R. M. (1986) Alterations in noradrenergic innervation of the brain following dorsal bundle lesions in neonatal rats. Brain Res. Bull. 16, 47–54.

    PubMed  CAS  Google Scholar 

  45. Nomura, Y. and Segawa, T. (1979) Striatal dopamine content reduced in developing rats treated with 6-hydroxydopa. Jpn. J. Pharmacol. 29, 306–309.

    PubMed  CAS  Google Scholar 

  46. Jaim-Etcheverry, G., Teitelman, G., and Zieher, L. M. (1975) Choline acetyltransferase activity increases in the brain stem of rats treated at birth with 6-hydroxydopa. Brain Res. 100, 699–704.

    PubMed  CAS  Google Scholar 

  47. Nomura, Y., Kajiyama, H., and Segawa, T. (1980) Hypersensitivity of cardiac betaadrenergic receptors after neonatal treatment of rats with 6-hydroxydopa. Eur. J. Pharmacol. 66, 225–232.

    PubMed  CAS  Google Scholar 

  48. Kajiyama, H., Obara, K., Nomura, Y., and Segawa, T. (1982) The increase of cardiac beta 1-subtype of beta-adrenergic receptors in adult rats following neonatal 6-hydroxydopa treatment. Eur. J. Pharmacol. 77, 75–77.

    PubMed  CAS  Google Scholar 

  49. Nomura, Y., Kajiyama, H., and Segawa, T. (1979) Decrease in muscarinic cholinergic response of the rat heart following treatment with 6-hydroxydopa. Eur. J. Pharmacol. 60, 323–327.

    PubMed  CAS  Google Scholar 

  50. Jaim-Etcheverry, G., Shoemaker, W. J., Zieher, L. M., and Bloom, F. E. (1980) Antiserum to nerve growth factor does not prevent the increase of brain stem noradrenaline after neonatal 6-hydroxydopa. Brain Res. 197, 547–553.

    PubMed  CAS  Google Scholar 

  51. Levi-Montalcini, R. and Angeletti, P. U. (1968) Nerve growth factor. Physiol. Rev. 48, 534–569.

    PubMed  CAS  Google Scholar 

  52. Kostrzewa, R. M. and Klisans-Fuenmayor, D. (1984) Development of an opioidspecific action of morphine in modifying recovery of neonatally-damaged noradrenergic fibers in rat brain. Res. Commun. Chem. Pathol. Pharmacol. 46, 3–11.

    PubMed  CAS  Google Scholar 

  53. Thoa, N. B., Eichelman, B., Richardson, J. S., and Jacobowitz, D. (1972) 6-Hydroxydopa depletion of brain norepinephrine and the function of aggressive behavior. Science 178, 75–77.

    Google Scholar 

  54. Richardson, J. S., Cowan, N., Hartman, R., and Jacobowitz, D. M. (1974) On the behavioral and neurochemical actions of 6-hydroxydopa and 5,6-dihydroxytryptamine in rats. Res. Commun. Chem. Pathol. Pharmacol. 8, 29–44.

    PubMed  CAS  Google Scholar 

  55. Morgan, D. N., McLean, J. H., and Kostrzewa, R. M. (1979) Effects of 6-hydroxydopamine and 6-hydroxydopa on development of behavior. Pharmacol. Biochem. Behay. 11, 309–312.

    CAS  Google Scholar 

  56. McLean, J. H., Kostrzewa, R. M., and May, J. G. (1976) Behavioral and biochemical effects of neonatal treatment of rats with 6-hydroxydopa. Pharmacol. Biochem. Behay. 4, 601–607

    CAS  Google Scholar 

  57. Nomura, Y. and Segawa, T. (1978) Apomorphine-induced locomotor stimulation in developing rats treated with 6-hydroxydopa. Eur. J. Pharmacol. 50, 153–156.

    PubMed  CAS  Google Scholar 

  58. Nomura, Y. and Oki, K. (1980) TRH-induced behavioral arousal in developing rats pretreated with 6-hydroxydopa. Pharmacol. Biochem. Behay. 12, 925–930.

    CAS  Google Scholar 

  59. Oh, K., Nomura, Y., and Segawa, T. (1982) Involvement of central noradrenergic system in thyrotropin-releasing hormone-induced behavioral excitement in 6-OHDOPA-treated, infant rats. J. Pharmacobiodyn. 5, 716–719.

    Google Scholar 

  60. Slater, P. and Blundell, C. (1978) The effects of a permanent and selective depletion of brain catecholamines on the antinociceptive action of morphine. Naunyn-Schmiedebergs Arch. Pharmacol. 305, 227–232.

    PubMed  CAS  Google Scholar 

  61. Kimura, T. (1957) Electromyographic studies of effects of chlorpromazine on nociceptively and proprioceptively induced reflex pattern of rabbits hindlimb. Jpn. J. Pharmacol. 6, 162–174.

    PubMed  CAS  Google Scholar 

  62. Cornwell-Jones, C. A. and Boilers, H. R. (1983) Neonatal 6-hydroxydopa alters con-specific odor investigation by male rats. Brain Res. 268, 291–294.

    PubMed  CAS  Google Scholar 

  63. Cornwell-Jones, C. A., Decker, M. W., Chang, J. W., Cole, B., Goltz, K. M., Tran, T., and McGaugh, J. L. (1989) Neonatal 6-hydroxydopa, but not DSP-4, elevates brainstem monoamines and impairs inhibitory avoidance learning in developing rats. Brain Res. 493, 258–268.

    PubMed  CAS  Google Scholar 

  64. McLean, J. H., Glasser, R. S., Kostrzewa, R. M., and May, J. G. (1980) Effects of neonatal 6-hydroxydopa on behavior in female rats. Pharmacol. Biochem. Behay. 13, 863–868.

    CAS  Google Scholar 

  65. Lin, J. Y., Mai, L. M., and Pan, J. T. (1993) Effects of systemic administration of 6-hydroxydopamine, 6-hydroxydopa and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on tuberoinfundibular dopaminergic neurons in the rat. Brain Res. 624, 126–130.

    PubMed  CAS  Google Scholar 

  66. Nomura, Y. and Segawa, T. (1978) Muscarinic hyposensitivity in the developing rat pretreated with 6-hydroxydopa. Eur. J. Pharmacol. 50, 431–435.

    PubMed  CAS  Google Scholar 

  67. Nomura, Y., Kajiyama, H., Nakata, Y., and Segawa, T. (1979) Muscarinic cholinergic binding in striatal and mesolimbic areas of the rat: Reduction by 6-hydroxydopa. Eur. J. Pharmacol. 58, 125–131.

    PubMed  CAS  Google Scholar 

  68. Agrup, G., Hansson, C., Rorsman, H., Rosengren, E., and Tegner, E. (1983) Methaemoglobin-catalysed formation of dopa and 6-OH-dopa from tyrosine. Acta. Derm. Venereol. 63, 152–155.

    PubMed  CAS  Google Scholar 

  69. Jonsson, G. and Sachs, C. (1973) Pharmacological modifications of the 6-hydroxyDOPA induced degeneration of central noradrenaline neurons. Biochem. Pharmacol. 22, 1709–1716.

    PubMed  CAS  Google Scholar 

  70. VonVoigtlander, P. E and Losey, E. G. (1978) 6-Hydroxydopa depletes both brain epinephrine and norepinephrine: Interactions with antidepressants. Life Sci. 23, 147–150.

    Google Scholar 

  71. Evans, J. M. and Cohen, G. (1989) Studies on the formation of 6-hydroxydopamine in mouse brain after administration of 2,4,5-trihydroxyphenylalanine (6-hydroxyDOPA). J. Neurochem. 52, 1461–1467.

    PubMed  CAS  Google Scholar 

  72. Evans, J. and Cohen, G. (1993) Catecholamine uptake inhibitors elevate 6-hydroxydopamine in brain after administration of 6-hydroxydopa. Fur. J. Pharmacol. 232, 241–245.

    CAS  Google Scholar 

  73. Biscoe, T. J., Evans, R. H., Headley, P. M., Martin, M. R., and Watkins, J. (1976) Structure activity relations of excitatory amino acids on frog and rat spinal neurones. Br. J. Pharmacol. 58, 373–382.

    PubMed  CAS  Google Scholar 

  74. Rosenberg, P. A., Loring, R., Xie, Y., Zaleskas, V., and Aizenman, E. (1991) 2,4,5trihydroxyphenylalanine in solution forms a non-N-methyl-D-aspartate glutamatergic agonist and neurotoxin. Proc. Natl. Acad. Sci. USA 88, 4865–4869.

    Google Scholar 

  75. Aizenman, E., White, W. F., Loring, R. H., and Rosenberg, P. A. (1990) A 3,4-dihydroxyphenylalanine oxidation product is a non-N-methyl-D-aspartate glutamatergic agonist in rat cortical neurons. Neurosci. Lett. 116, 168–171.

    PubMed  CAS  Google Scholar 

  76. Cha, J.-H. J., Dure, J. L. S., IV, Sakurai, S. Y., Penney, J. B., and Young, A. B. (1991) 2,4,5-Trihydroxyphenylalanine (6-hydroxy-DOPA) displaces [3H]AMPA binding in rat striatum. Neurosci. Lett. 132, 55–58.

    Google Scholar 

  77. Kunig-G., Hartmann, J., Niedermeyer, G., Deckert, J., Ransmayr, G., Heinsen, H., Beckmann, H., and Riederer, P. (1994) Excitotoxins L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenylalanine (6-OH-DOPA) inhibit [3H] alpha-amino3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) binding in human hippocampus. Neurosci. Lett. 169, 219–222.

    Google Scholar 

  78. Aizenman, E., Boeckman, R A., and Rosenberg, P. A. (1992) Glutathione prevents 2,4,5trihydroxyphenylalanine excitotoxicity by maintaining it in a reduced, non-active form. Neurosci. Lett. 144, 233–236.

    PubMed  CAS  Google Scholar 

  79. Nappi, A. J. and Vass, E. (1994) The effects of glutathione and ascorbic acid on the oxidations of 6-hydroxydopa and 6-hydroxydopamine Biochem. Biophys. Acta 1201, 498–504.

    PubMed  Google Scholar 

  80. Newcomer, T.A., Rosenberg, P.A., and Aizenman, E. (1995) Iron-mediated oxidation of 3,4-dihydroxyphenylalanine to an excitotoxin. J. Neurochem. 64, 1742–1748.

    PubMed  CAS  Google Scholar 

  81. Rodriguez-Lopez, J. N., Banon-Arnao, M., Martinez-Ortiz, F., Tudela, J., Acosta, M., Varon, R., and Garcia-Canovas, E (1992) Catalytic oxidation of 2,4,5-trihydroxyphenylalanine by tyrosinase: identification and evolution of intermediates. Biochim. Biophys. Acta 1160, 221–228.

    PubMed  CAS  Google Scholar 

  82. Lode, H. N., Bruchelt, G., Rieth, A. G., and Niethammer, D. (1990) Release of iron from ferritin by 6-hydroxydopamine under aerobic and anaerobic conditions. Free Radical Res. Commun. 11, 153–158.

    CAS  Google Scholar 

  83. Kano, K., Mori, T., Uno, B., Goto, M., and Ikeda, T. (1993) Characterization of topa quinone cofactor. Biochim. Biophys. Acta 1157, 324–331.

    PubMed  CAS  Google Scholar 

  84. Newcomer, T. A., Palmer, A. M., Rosenberg, P. A., and Aizenman, E. (1993) Nonenzymatie conversion of 3,4-dihydroxyphenylalanine to 2,4,5-trihydroxyphenylalanine and 2,4,5-trihydroxyphenylalanine quinone in physiological solutions. J. Neurochem. 61, 911–920.

    PubMed  CAS  Google Scholar 

  85. Skaper, S. D., Negro, A., Facci, L., and Dal-Toso, R. (1993) Brain-derived neurotrophic factor selectively rescues mesencephalic dopaminergic neurons from 2,4,5-trihydroxyphenylalanine-induced injury. J. Neurosci. Res. 34, 478–487.

    PubMed  CAS  Google Scholar 

  86. Follenius, E. (1971) Action de la 6 OH dopamine sur les melanophores et sur l’adaptation chromatique chez le poisson teleosteen Gasterosteus aculeatus. Comptes Rendes Acad. Sci. 272, 733–736.

    CAS  Google Scholar 

  87. Wick, M. M. (1978) Dopamine: a novel antitumor agent active against B-16 melanoma in vivo. J. Invest. Dermatol. 71, 163, 164.

    Google Scholar 

  88. Wick, M. M., Byers, L., and Ratliff, J. (1979) Selective toxicity of 6-hydroxydopa for melanoma cells. J. Invest. Dermatol. 72, 67–69.

    PubMed  CAS  Google Scholar 

  89. Hansson, C., Rorsman, H., Rosengren, E., and Wittbjer, A. (1985) Production of 6-hydroxydopa by human tyrosinase. Acta Derm. Venereol. 65, 154–157.

    PubMed  CAS  Google Scholar 

  90. Morrison, M. E., Yagi, M. J., and Cohen, G. (1985) In vitro studies of 2,4-dihydroxyphenylalanine, a prodrug targeted against malignant melanoma cells. Proc. Natl. Acad. Sci. USA 82, 2960–2964.

    PubMed  CAS  Google Scholar 

  91. Agrup, P., Carstam, R., Wittbjer, A., Rorsman, H., and Rosengren, E. (1989) Tyrosinase activity in serum from patients with malignant melanoma. Acta Derm. Venereol. 69, 120–124.

    PubMed  CAS  Google Scholar 

  92. Passi, S., Picardo, M., and Nazzaro-Porro, M. (1987) Comparative cytotoxicity of phenols in vitro. Biochem. J. 245, 537–542.

    PubMed  CAS  Google Scholar 

  93. Metodiewa, D., Reszka, K., and Dunford, H. B. (1989) Oxidation of the substituted catechols dihydroxyphenylalanine methyl ester and trihydroxyphenylalanine by lactoperoxidase and its compounds. Arch. Biochem. Biophys. 274, 601–608.

    PubMed  CAS  Google Scholar 

  94. Rossi, A., Petruzzelli, R., and Agro, A. E (1992) cDNA-derived amino-acid sequence of lentil seedlings’ amine oxidase. FEBS Lett. 301, 253–257.

    Google Scholar 

  95. Cooper, R. A., Knowles, P. E, Brown, D. E., McGuirl, M. A., and Dooley, D. M. (1992) Evidence for copper and 3,4,6-trihydroxyphenylalanine quinone cofactors in an amine oxidase from the gram-negative bacterium Escherichia coli K-12. Biochem. J. 288, 337–340.

    PubMed  CAS  Google Scholar 

  96. Plastino, J. and Klinman, J. P. (1995) Limited proteolysis of Hansenula polymorpha yeast amine oxidase: Isolation of a C-terminal fragment containing both a copper and quinocofactor. FEBS Lett. 371, 276–278.

    PubMed  CAS  Google Scholar 

  97. Schilling, B. and Lerch, K. (1995) Amine oxidases from Aspergillus niger: Identification of a novel flavin-dependent enzyme. Biochim. Biophys. Acta 1233, 529–537.

    Google Scholar 

  98. Brown, D. E., McGuirl, M. A., Dooley, D. M., Janes, S. M., Mu, D., and Klinman, J. P. (1991) The organic functional group in cooper-containing amine oxidases. Resonance Raman spectra are consistent with the presence of topa quinone (6-hydroxydopa quinone) in the active site. J. Biol. Chem. 266, 4049–4051.

    PubMed  CAS  Google Scholar 

  99. Greenaway, F. T., O’Gara, C. Y., Marchena, J. M., Poku, J. W., Urtiaga, J. G., and Zou, Y. (1991) EPR studies of spin-labeled bovine plasma amine oxidase: The nature of the substrate-binding site. Arch. Biochem. Biophys. 285, 291–296.

    PubMed  CAS  Google Scholar 

  100. Mu, D., Medzihradszky, K. E, Adams, G. W., Mayer, P., Hines, W. M., Burlingame, A. L., Smith, A. J., Cai, D., and Klinman, J. P. (1994) Primary structures for a mammalian cellular and serum copper amine oxidase. J. Biol. Chem. 269, 9926–9932.

    PubMed  CAS  Google Scholar 

  101. Mu, D., Janes, S. M., Smith, A. J., Brown, D. E., Dooley, D. M., and Klinman, J. P. (1992) Tyrosine codon corresponds to topa quinone at the active site of copper amine oxidases. J. Biol. Chem. 267, 7979–7982.

    PubMed  CAS  Google Scholar 

  102. McIntire, W. S. (1994) Quinoproteins. FASEB J. 8, 513–521.

    PubMed  CAS  Google Scholar 

  103. Pedersen, J. Z., el-Sherbini, S., Finazzi-Agro, A., and Rotilio, G. (1992) A substrate-cofactor free radical intermediate in the reaction mechanism of copper amine oxidase. Biochemistry 31, 8–12.

    PubMed  CAS  Google Scholar 

  104. Dooley, D. M., McGuirl, M. A., Brown, D. E., Turowski, P. N., McIntire, W. S., and Knowles, P. F. A Cu(I)-semiquinone state in substrate-reduced amine oxidases. Nature 349, 262–264.

    Google Scholar 

  105. Matsuzaki, R., Suzuki, S., Yamaguchi, K., Fukui, T., and Tanizawa, K. (1995) Spectroscopic studies on the mechanism of the topa quinone generation in bacterial monoamine oxidase. Biochemistry 34, 4524–4530.

    PubMed  CAS  Google Scholar 

  106. Janes, S. M. and Klinman, J. P. (1991) An investigation of bovine serum amine oxidase active site stoichiometry: Evidence for an aminotransferase mechanism involving two carbonyl cofactors per enzyme dimer. Biochemistry 30, 4599–4605.

    PubMed  CAS  Google Scholar 

  107. Bellelli, A., Finazzi Agro, A., Floris, G., and Brunori, M. (1991) On the mechanism and rate of substrate oxidation by amine oxidase from lentil seedlings. J. Biol. Chem. 266, 20,654–20, 657.

    Google Scholar 

  108. Dooley, D. M., McIntire, W. S., McGuirl, M. A., Cote, C. E., and Bates, J. L. (1990) Characterization of the active site of Arthrobacter PI methylamine oxidase: evidence for copper—quinone interactions. J. Am. Chem. Soc. 112, 2782–2789.

    CAS  Google Scholar 

  109. Weiss, J. H., Koh, J. Y., and Choi, D. W. (1989) Neurotoxicity of beta-N-methylaminoL-alanine (BMAA) and beta-N-oxalylamino-L-alanine (BOAA) on cultured cortical neurons. Brain Res. 497, 64–71.

    PubMed  CAS  Google Scholar 

  110. Caine, D. B., McGeer, E., Eisen, A., and Spencer, P. (1986) Alzheimer’s disease, Parkinson’s disease and motoneurone disease: abiotrophic interaction between ageing and environment. Lancet ii, 1067–1070.

    Google Scholar 

  111. Kurland, L. T. (1988) Amyotrophic lateral sclerosis and Parkinson’s disease complex on Guam linked to an environmental neurotoxin. Trends Neurosci. 11, 51–54.

    PubMed  CAS  Google Scholar 

  112. Meldrum, B. and Garthwaite, J. (1991) Excitatory amino acid neurotoxicity and neurodegenerative disease, in The Pharmacology of Excitatory Amino Acids (Lodge, D. and Collingridge, G. L., eds. ), A TiPS Special Report, pp. 54–61.

    Google Scholar 

  113. Meldrum, B. and Garthwaite, J. (1991) Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol. Sci. 11, 379–387

    Google Scholar 

  114. Spencer, P. S., Ludolph, A., Dwivedi, M. R, Roy, D. N., Hugon, J., and Schaumburg, H. H. (1986) Lathyrism: evidence for role of the neuroexcitatory amino acid BOAA. Lancet 2, 1066–1067.

    PubMed  CAS  Google Scholar 

  115. Skaper, S. D., Facci, L., Sciavo, N., Vantini, G., Moroni, E, Dal Toso, R., and Leon, A. (1992) Characterization of 2,4,5-trihydroxyphenylalanine neurotoxicity in vitro and protective effects of ganglioside GM1: Implications for Parkinson’s disease. J. Pharmacol. Exp. Ther. 263, 1440–1446.

    PubMed  CAS  Google Scholar 

  116. Murase, K., Hattori, A., Kohno, M., and Hayashi, K. (1993) Stimulation of nerve growth factor synthesis/secretion in mouse astroglial cells by coenzymes. Biochem. Mol. Biol. Int. 30, 615–621.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Richard M. Kostrzewa
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kostrzewa, R.M. (1998). 6-Hydroxydopa, a Catecholamine Neurotoxin and Endogenous Excitotoxin at Non-NMDA Receptors. In: Kostrzewa, R.M. (eds) Highly Selective Neurotoxins. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-477-1_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-477-1_4

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-047-2

  • Online ISBN: 978-1-59259-477-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation