Participation of peroxynitrite in acetylcholine release induced by nitric oxide generators.
Peroxynitrite is a product produced by spontaneous reaction of nitric oxide (NO) with superoxide. Functional roles of peroxynitrite in the release of endogenous acetylcholine evoked by NO generators has been examined using primary-cultured cerebral cortical neurons. NO generators, such as sodium nitroprusside and S-nitroso-N-acetylpenicillamine, dose-dependently increased the release of acetylcholine (ACh); such increase of the release was significantly suppressed by hemoglobin which has the capacity to abolish biological effects of NO. Two types of superoxide scavengers, Cu2+, Zn2+ superoxide dismutase and ceruloplasmin, significantly reduced the NO-evoked ACh release. These results indicate that NO requires superoxide to evoke the release of ACh. Synthesized peroxynitrite evoked the release of ACh from cerebral cortical neurons in a dose-dependent manner. Thus, it is indicated that the NO-evoked ACh release is mediated, at least in part, by peroxynitrite produced by the reaction of NO with superoxide.
Ohkuma
S
S
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Katsura
M
M
Guo
J L
JL
Hasegawa
T
T
Kuriyama
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002570:Ceruloplasmin / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D006454:Hemoglobins; D009566:Nitrates; D014665:Vasodilator Agents; D013481:Superoxides; D009599:Nitroprusside; C039642:peroxynitric acid; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase; D002570:Ceruloplasmin; D010396:Penicillamine; D000109:Acetylcholine