In vivo trapping of hydroxyl free radicals in the striatum utilizing intracranial microdialysis perfusion of salicylate: effects of MPTP, MPDP+, and MPP+.
Increased formation of hydroxyl free radicals (.OH) reflected by .OH adduct of salicylate in brain dialysate was demonstrated during the sustained (more than 2 hours) dopamine overflow elicited by 75 nmol of 1-methyl-4-phenyldihydropyridine (MPDP+) and 1-methyl-4-phenylpyridinium (MPP+) in the rat striatum. Owing to its weak dopamine releasing action, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) did not significantly increase the .OH formation. This data suggests that sustained elevation of dopamine in the extracellular fluid elicited by MPTP analogues can be auto-oxidized, which in turn leads (possibly by indirect mechanisms) to the formation of cytotoxic .OH free radicals near the nigrostriatal terminals.
Obata
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National Institute of Neurological Disorders and Stroke, Bethesda, Md.
Chiueh
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000502:physiology; D005609:Free Radicals; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D010477:Perfusion; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000494:pharmacology*; D020156:Salicylic Acid; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D005609:Free Radicals; D006878:Hydroxides; D011726:Pyridinium Compounds; D012459:Salicylates; D017665:Hydroxyl Radical; C026560:1-(4-methoxyphenyl)pyridinium; C044755:1-methyl-4-phenyl-2,3-dihydropyridinium; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D020156:Salicylic Acid; D004298:Dopamine