Antioxidant property of pramipexole independent of dopamine receptor activation in neuroprotection.
Pramipexole and several other dopamine agonists have been recently demonstrated to have neuroprotective effects in vitro and in vivo. We report here that pramipexole can protect DAergic cell line MES 23.5 against dopamine (DA), 6-hydroxydopamine (6-OHDA), and hydrogen peroxide (H2O2)-induced cytotoxicity in vitro possibly through antioxidant effects, and such neuroprotection could not be blocked by selective D2 or D3 antagonists. Incubation with pramipexole (5-20 microM) in MES 23.5 cell cultures increased cellular levels of glutathione (GSH), and elevated glutathione peroxidase (GSH-Px) and catalase activities, but only marginally enhanced SOD activity. Pretreatment with D2 or D3 antagonists did not block the stimulating effects of pramipexole on the cellular levels of GSH, and on the activities of GSH-Px and catalase in MES 23.5 cells. These results indicate that pramipexole's neuroprotective effects are likely associated with its antioxidant property independent of D2/D3 receptor activation.
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Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA. Weidong@bcm.tmc.edu
Jankovic
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Xie
W
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Appel
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D052160:Benzothiazoles; D002460:Cell Line / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000077487:Pramipexole; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D050637:Receptors, Dopamine D3; D013844:Thiazoles / Q000494:pharmacology*
D000975:Antioxidants; D052160:Benzothiazoles; D065127:Dopamine D2 Receptor Antagonists; D018696:Neuroprotective Agents; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013844:Thiazoles; D000077487:Pramipexole; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D004298:Dopamine