Scavenging effects of dopamine agonists on nitric oxide radicals

Sakiko Nishibayashi, Masato Asanuma, Masahiro Kohno, Marvin Gómez-Vargas, Norio Ogawa

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

It has recently been considered that free radicals are closely involved in the pathogenesis of Parkinson's disease (PD), and the level of nitric oxide radical (·NO), one of the free radicals, is reported to increase in PD brain. In the present study, we established a direct detection system for ·NO in an in vitro ·NO generating system using 3-(2 hydroxy-1-methylethyl- 2-nitrosohydrazino)-N-methyl-1-propanamine as an ·NO donor and 2-(4- carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO) by electron spin resonance (ESR) spectrometry and examined the quenching effects of the dopamine agonists pergolide and bromocriptine on the amount of ·NO generated. ·NO appeared to be scavenged by pergolide and, to a lesser extent, by bromocriptine. In the competition assay, the 50% inhibitory concentration values for pergolide and bromocriptine were estimated to be ~23 and 200 μM, respectively. It was previously reported that in vivo treatment of pergolide and bromocriptine completely protected against the decrease in levels of striatal dopamine and its metabolites in the 6- hydroxydopamine-injected mouse. Considering these findings, pergolide and probably bromocriptine may also protect against dysfunction of dopaminergic neurons because of its multiple effects; not only does it stimulate the presynaptic autoreceptors, but it also directly scavenges ·NO radicals and hence protects against ·NO-related cytotoxicity. This ESR spectrometry method using carboxy-PTIO may be useful for screening other drugs that can quench ·NO.

Original languageEnglish
Pages (from-to)2208-2211
Number of pages4
JournalJournal of Neurochemistry
Volume67
Issue number5
DOIs
Publication statusPublished - Nov 1996

Keywords

  • 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3- oxide
  • Dopamine agonist
  • Electron spin resonance
  • Free radical
  • Nitric oxide
  • Pergolide
  • Scavenging effect

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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