Dopamine agonist pergolide prevents levodopa-induced quinoprotein formation in parkinsonian striatum and shows quenching effects on dopamine-semiquinone generated in vitro.
The neurotoxicity of dopamine (DA) quinones that appears in dopaminergic neuron-specific oxidative stress has recently been shown to play a role in the pathogenesis and/or progression of Parkinson disease. To clarify the effects of a DA agonist, pergolide, on the levodopa-induced elevation of quinones, the authors examined striatal changes in quinoprotein using a hemi-parkinsonian mouse model. The level of striatal quinoprotein was significantly elevated specifically on the parkinsonian side, but not on the control side, after repeated levodopa administration. This levodopa-induced increase in striatal quinoprotein was almost completely suppressed by adjunctive administration with pergolide on the lesioned side. Furthermore, it was clarified that pergolide scavenged DA-semiquinones generated in vitro in a dose-dependent manner. These suppressive and quenching effects of pergolide against cytotoxic DA quinones may play a key role in its neuroprotective mechanism in the parkinsonian brain.
Miyazaki
Ikuko
I
Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
Asanuma
Masato
M
Diaz-Corrales
Francisco J
FJ
Miyoshi
Ko
K
Ogawa
Norio
N
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D007839:Functional Laterality / Q000502:physiology; D007980:Levodopa / Q000009:adverse effects*; D051379:Mice; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents; D020258:Neurotoxicity Syndromes / Q000188:drug therapy; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D010479:Pergolide / Q000494:pharmacology*; D011485:Protein Binding; D011809:Quinones / Q000378:metabolism*; D013565:Sympatholytics
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D018696:Neuroprotective Agents; D011809:Quinones; D013565:Sympatholytics; D010479:Pergolide; D007980:Levodopa; D016627:Oxidopamine; D004298:Dopamine