Potassium chloride depolarization enhances MPP+-induced hydroxyl radical generation in the rat striatum.
We determined that extracellular potassium ion concentration, [K+]o-induced depolarization, enhances 1-methyl-4-phenylpyridinium ion (MPP+)-induced hydroxyl radical (*OH) generation in the rat striatum. Rats were anesthetized, and sodium salicylate in Ringer's solution (0.5 nmol/microl/min) was infused through a microdialysis probe to detect the generation of *OH as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. Induction of high concentration KCl (70 mM) drastically increased formation of *OH trapped as DHBA by the action of MPP+. When dopamine (DA) was administered to the high KCl-treated animals, a marked elevation of DHBA was observed, compared with MPP+-only-treated animals, that showed a positive linear correlation between DA and *OH formation trapped as DHBA (R2 = 0.979) in the dialysate. When corresponding experiments were performed with iron (II), the same results were obtained: a positive linear correlation between the release of iron (II) and DHBA (R2 = 0.988) in the dialysate. These results suggest that [K+]o-induced depolarization enhances the formation of *OH products of efflux/oxidation due to MPP+.
Obata
T
T
Department of Pharmacology, Oita Medical University, Japan. tobata@oita-med.ac.jp
Aomine
M
M
Yamanaka
Y
Y
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006540:Herbicides / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D007501:Iron / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017551:Microdialysis; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012980:Sodium Salicylate / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D006540:Herbicides; D017665:Hydroxyl Radical; D011189:Potassium Chloride; D007501:Iron; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D012980:Sodium Salicylate