Nitric oxide-induced [3H] GABA release from cerebral cortical neurons is mediated by peroxynitrite.
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.
Ohkuma
S
S
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Narihara
H
H
Katsura
M
M
Hasegawa
T
T
Kuriyama
K
K
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*
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