title: 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.
authors.affiliation: Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ohkuma
authors.forename: H
authors.initials: H
authors.lastname: Narihara
authors.forename: M
authors.initials: M
authors.lastname: Katsura
authors.forename: T
authors.initials: T
authors.lastname: Hasegawa
authors.forename: K
authors.initials: K
authors.lastname: Kuriyama
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002570:Ceruloplasmin / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase / Q000494:pharmacology; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D009566:Nitrates; D014316:Tritium; D009599:Nitroprusside; C039642:peroxynitric acid; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase; D002570:Ceruloplasmin; D010396:Penicillamine