Protective effect of histidine on potassium chloride depolarization enhances 1-methyl-4-phenylpyridinium ion-induced hydroxyl radical generation in the rat striatum.
The present study examined the antioxidant effect of histidine on 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/M microl/min) was infused through a microdialysis probe to detect the generation of *OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. Induction of [K+]o (20, 70 and 140 mM) significantly increased the level of 2,3-DHBA by the action of MPP+ (5 mM) in a concentration-dependent manner. However, histidine (25 mM) reduced the [K+]o-induced *OH formation. Although the level of MPP+-induced dopamine (DA) and 2,3-DHBA formation after [K+]o (70 mM) treatment increased, [K+]o failed to increase either the level of MPP+-induced DA and 2,3-DHBA in the reserpinized group. When iron (II) was administered to [K+]o (70 mM)-pretreated rats, iron (II) clearly produced a dose-dependent increase in the level of 2,3-DHBA, as compared with MPP+-only treated rats. However, in the presence of histidine (25 mM), the effect of [K+]o was abolished. These results indicated that histidine may reduce the [K+]o-induced depolarization enhanced *OH formation by the action of MPP+ in the rat striatum.
Obata
T
T
Department of Pharmacology, Oita Medical University, Japan. tobata@oita-med.ac.jp
Yamanaka
Y
Y
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D006639:Histidine / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology; D013565:Sympatholytics / Q000494:pharmacology
D013565:Sympatholytics; D017665:Hydroxyl Radical; D006639:Histidine; D011189:Potassium Chloride; D012110:Reserpine; D007501:Iron; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine