In vitro generation and decomposition of S-nitrosothiols from direct and indirect nitric oxide donors.
Nitric oxide which was released in aqueous solutions (> or = 10 microM) of direct NO-donors such as 3-morpholinesydnonimine (SIN-1) and S-nitroso-N-acetyl-penicillamine (SNAP) consumed avidly sulfhydryl groups of N-acetylcysteine > cysteine > glutathione. In case of SIN-1 generation of nitrites run in parallel to disappearance of sulfhydryl groups of N-acetylcysteine and glutathione, however, for a pair of SIN-1 and cysteine the rate of formation of nitrites was much slower than the rate of consumption of sulfhydryl groups. We infer that kinetics of formation and breakdown of S-nitrosothiols varies depending on the type of a thiol which reacts with a NO-donor. Indirect NO-donors such as glyceryl trinitrate (GTN), molsidomine (MSD) or sodium nitroprusside (NaNP) at concentrations < 100 microM did not consume sulfhydryl groups of cysteine unless pretreated with the xanthine/xanthine oxidase system. We suppose that in this last case superoxide anions react with nitric oxide to form peroxynitrites with a higher potency than nitric oxide itself to destroy sulfhydryl groups. We conclude that out of three studied thiols N-acetylcysteine is the best substrate for the formation of S-nitrosothiols, while S-nitrosocysteine is the slowest releaser of nitric oxide. Moreover, unlike SIN-1 and SNAP, NaNP is not a direct NO-donor but behaves rather like GTN. Minute amounts of nitric oxide released either from NaNP or GTN gain from superoxide anions an amplification as SH-scavengers.
Robak
J
J
Department of Pharmacology, Medical College, Jagiellonian University, Kraków, Poland.
Gryglewski
R J
RJ
D007202:Indicators and Reagents; D007700:Kinetics; D008623:Mercaptoethanol; D009569:Nitric Oxide / Q000737:chemistry*; D009603:Nitroso Compounds / Q000737:chemistry*; D026403:S-Nitrosothiols; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013481:Superoxides
D007202:Indicators and Reagents; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D013438:Sulfhydryl Compounds; D013481:Superoxides; D009569:Nitric Oxide; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol