Nitric Oxide-Induced [3H]GABA Release from Cerebral Cortical Neurons Is Mediated by Peroxynitrite

Abstract: The functional significance of peroxynitrite in the release of ³H]GABA induced by nitric oxide (NO) liberated from NO generators was investigated using cerebral cortical neurons in primary culture. NO generators such as sodium nitroprusside (SNP) and S -nitroso- N -acetylpenicillamine (SNAP) increased ³H]GABA release in a dose-dependent manner. These increases in ³H]GABA release were significantly inhibited by hemoglobin, indicating that those NO generators evoke the release of ³H]GABA by the formation of NO. Two types of superoxide scavengers, Cu²⁺/Zn²⁺ superoxide dismutase and ceruloplasmin, significantly reduced the increase in ³H]GABA release induced by both SNP and SNAP, which assumes that NO requires superoxide to induce ³H]GABA release from the neurons. In addition, synthesized peroxynitrite induced a dose-dependent increase in ³H]GABA release from the neurons. These results indicate that NO-induced ³H]GABA release is mediated by peroxynitrite formed by the reaction of NO with superoxide.