Current Perspective : Nitric Oxide and Depolarization Induce Hydroxyl Radical Generation

概要

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Nitric oxide (NO) contributes to the extracellular potassium-ion concentration ([K+]o)-induced hydroxyl radical (•OH) generation. Cytotoxic free radicals such as peroxinitrite (ONOO−) and •OH may also be implicated in NO-mediated cell injury. NO is synthesized from <sc>L</sc>-arginine by NO synthase (NOS). NOS activation was induced by K+ depolarization. Oxidative modification of low-density lipoprotein (LDL) is thought to contribute to the production of oxygen derived-free radicals. However, LDL oxidation may be related to noradrenaline-induced •OH generation, but LDL oxidation may be unrelated to •OH generation via NOS activation. Abnormal levels of extracellular free dopamine (DA) and/or intraneuronal Ca2+ triggered by 1-methyl-4-phenylpyridinium ion (MPP+) may be detrimental to the functioning of dopaminergic nerve terminals in the striatum. Although [K+]o-induced depolarization enhances the formation of •OH product due to MPP+, the •OH generation via NOS activation may be unrelated to the DA-induced •OH generation. Depolarization enhances the formation of •OH products via NOS activation.
社団法人日本薬理学会の論文
2002-01-01