Role of peroxynitrite in [3H] gamma-aminobutyric acid release evoked by nitric oxide and its mechanism.

Role of peroxynitrite in [3H] gamma-aminobutyric acid (GABA) release evoked by N-methyl-D-aspartate (NMDA) and S-nitroso-N-acetyl-penicillamine (SNAP) and mechanisms of [3H]GABA release induced by peroxynitrite in comparison with those induced by NMDA and SNAP were investigated using cerebrocortical neurons. NMDA dose dependently increased [3H]GABA release, which was significantly inhibited by hemoglobin and superoxide scavengers, Cu2+, Zn(2+)-superoxide dismutase and ceruloplasmin. The NMDA-evoked [3H]GABA release was significantly suppressed by GABA transport inhibitors and inhibitors of voltage-dependent L-typed Ca2+ channel. The SNAP-evoked [3H]GABA release was significantly reduced by Ca2+ withdrawal and by GABA transport inhibitors either in the presence or absence of Ca2+. Similar patterns of [3H]GABA release induced by peroxynitrite were observed. These results indicate that peroxynitrite formed by the reaction of NO with superoxide participates, in part, in the release of [3H]GABA induced by NMDA and SNAP.