Nitric oxide and depolarization induce hydroxyl radical generation.

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 L-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.