6-hydroxydopamine increases the hydroxylation and nitration of phenylalanine in vivo: implication of peroxynitrite formation.

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  • Additional Information
    • Source:
      Publisher: Wiley on behalf of the International Society for Neurochemistry Country of Publication: England NLM ID: 2985190R Publication Model: Print Cited Medium: Print ISSN: 0022-3042 (Print) Linking ISSN: 00223042 NLM ISO Abbreviation: J Neurochem Subsets: MEDLINE
    • Publication Information:
      Publication: 2001- : Oxford, UK : Wiley on behalf of the International Society for Neurochemistry
      Original Publication: New York : Raven Press
    • Subject Terms:
    • Abstract:
      In the present study, we investigated the effect of the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) on hydroxyl free radical and peroxynitrite formation in vivo using D-phenylalanine as a novel mechanistic probe. In vivo microdialysis was carried out in the striatum of freely moving male Wistar rats. The microdialysis probes were perfused with artificial cerebrospinal fluid containing 5 mM D-phenylalanine (flow rate 2 microL/min). After obtaining a stable baseline 6-OHDA was delivered into the striatum via reverse microdialysis for 60 min. HPLC measurements of the effluent were performed using photodiode array detection for determination of phenylalanine derived o-tyrosine and m-tyrosine (as hydroxylation markers) as well as of nitrotyrosine and nitrophenylalanine (as nitration markers). The basal levels of the hydroxylation derived products of phenylalanine were approximately 100-fold higher than those of the nitration derived products. 6-OHDA (0.1, 1, 10 mM) significantly increased o- and m-tyrosine up to nine- and 13-fold, respectively, whereas levels of 3-nitrotyrosine and 4-nitrophenylalanine were significantly increased up to 422- and 358-fold, respectively. The results demonstrate that phenylalanine is a sensitive in vivo marker for 6-OHDA-induced hydroxylation and nitration reactions which are clearly concentration dependent. We conclude that peroxynitrite formation is involved in 6-OHDA-induced neurochemical effects.
    • Accession Number:
      0 (Adrenergic Agents)
      0 (Nitrates)
      0 (Oxidants)
      26404-66-0 (peroxynitric acid)
      47E5O17Y3R (Phenylalanine)
      8HW4YBZ748 (Oxidopamine)
      VTD58H1Z2X (Dopamine)
    • Publication Date:
      Date Created: 20010803 Date Completed: 20010830 Latest Revision: 20190630
    • Publication Date:
      20231215
    • Accession Number:
      10.1046/j.1471-4159.2001.00429.x
    • Accession Number:
      11483653