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 language | English |
|---|---|
| Pages (from-to) | 2208-2211 |
| Number of pages | 4 |
| Journal | Journal of Neurochemistry |
| Volume | 67 |
| Issue number | 5 |
| Publication status | Published - Nov 1996 |
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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
Cite this
Scavenging effects of dopamine agonists on nitric oxide radicals. / Nishibayashi, Sakiko; Asanuma, Masato; Kohno, Masahiro; Gómez-Vargas, Marvin; Ogawa, Norio.
In: Journal of Neurochemistry, Vol. 67, No. 5, 11.1996, p. 2208-2211.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Scavenging effects of dopamine agonists on nitric oxide radicals
AU - Nishibayashi, Sakiko
AU - Asanuma, Masato
AU - Kohno, Masahiro
AU - Gómez-Vargas, Marvin
AU - Ogawa, Norio
PY - 1996/11
Y1 - 1996/11
N2 - 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.
AB - 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.
KW - 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3- oxide
KW - Dopamine agonist
KW - Electron spin resonance
KW - Free radical
KW - Nitric oxide
KW - Pergolide
KW - Scavenging effect
UR - http://www.scopus.com/inward/record.url?scp=0029845289&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029845289&partnerID=8YFLogxK
M3 - Article
VL - 67
SP - 2208
EP - 2211
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 5
ER -