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

Abstract Role of peroxynitrite in [ 3 H]γ-aminobutyric acid (GABA) release evoked by N -methyl- d -aspartate (NMDA) and S -nitroso- N -acetyl-penicillamine (SNAP) and mechanisms of [ 3 H]GABA release induced by peroxynitrite in comparison with those induced by NMDA and SNAP were investigated using cerebrocortical neurons. NMDA dose dependently increased [ 3 H]GABA release, which was significantly inhibited by hemoglobin and superoxide scavengers, Cu 2+ , Zn 2+ -superoxide dismutase and ceruloplasmin. The NMDA-evoked [ 3 H]GABA release was significantly suppressed by GABA transport inhibitors and inhibitors of voltage-dependent L-typed Ca 2+ channel. The SNAP-evoked [ 3 H]GABA release was significantly reduced by Ca 2+ withdrawal and by GABA transport inhibitors either in the presence or absence of Ca 2+ . Similar patterns of [ 3 H]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 [ 3 H]GABA induced by NMDA and SNAP.