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Scavenging Effects of Dopamine Agonists on Nitric Oxide Radicals
Author(s) -
Nishibayashi Sakiko,
Asanuma Masato,
Kohno Masahiro,
GómezVargas Marvin,
Ogawa Norio
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67052208.x
Subject(s) - scavenging , nitric oxide , dopamine , radical , chemistry , neuroscience , pharmacology , medicine , biochemistry , biology , antioxidant , organic chemistry
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 µ M , 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.