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.
Ohkuma
S
S
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan. ff
Katsura
M
M
Guo
J L
JL
Narihara
H
H
Hasegawa
T
T
Kuriyama
K
K
D000818:Animals; D002478:Cells, Cultured; D002570:Ceruloplasmin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013482:Superoxide Dismutase / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D009566:Nitrates; C039642:peroxynitric acid; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase; D002570:Ceruloplasmin; D000254:Sodium-Potassium-Exchanging ATPase; D010396:Penicillamine