H(2)S and HS(-) donor NaHS releases nitric oxide from nitrosothiols, metal nitrosyl complex, brain homogenate and murine L1210 leukaemia cells.
Nitrosoglutathione [(GSNO), 500 nmol/l] relaxed the norepinephrine precontracted rat aortic rings. The relaxation effect was pronouncedly enhanced by H(2)S- and HS(-)-donor NaHS (30 micromol/l) at 7.5 pH but not at 6.3 pH. To study molecular mechanism of this effect, we investigated whether NaHS can release NO from NO donors. Using an electron paramagnetic resonance spectroscopy method of spin trap and by measuring the NO oxidation product, which is nitrite, by the Griess reaction, we report that NaHS released NO from nitrosothiols, namely from GSNO, S-nitroso-N-acetyl-DL: -penicillamine (SNAP), from metal nitrosyl complex nitroprusside (SNP) and from rat brain homogenate and murine L1210 leukaemia cells. From the observation that the releasing effect was more pronounced at 8.0 pH than 6.0 pH, we suppose that HS(-), rather than H(2)S, is responsible for the NO-releasing effect. Since in mammals, H(2)S and HS(-) are produced endogenously, we assume that their effect to release NO from nitrosothiols and from metal nitrosyl complexes are responsible for some of their biological activities and that this mechanism may be involved in S-nitrosothiol-signalling reactions.
Ondrias
Karol
K
Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlarska 5, 833 34, Bratislava, Slovak Republic. karol.ondrias@savba.sk
Stasko
Andrej
A
Cacanyiova
Sona
S
Sulova
Zdena
Z
Krizanova
Olga
O
Kristek
Frantisek
F
Malekova
Lubica
L
Knezl
Vladimir
V
Breier
Albert
A
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D006162:Guanylate Cyclase / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007939:Leukemia L1210 / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine / Q000378:metabolism; D026422:S-Nitrosoglutathione / Q000378:metabolism; D026403:S-Nitrosothiols / Q000378:metabolism*; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase; D013440:Sulfides / Q000494:pharmacology*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology
D020030:Nitric Oxide Donors; D009573:Nitrites; D018160:Receptors, Cytoplasmic and Nuclear; D026403:S-Nitrosothiols; D013440:Sulfides; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D026423:S-Nitroso-N-Acetylpenicillamine; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; C025451:sodium bisulfide; D006862:Hydrogen Sulfide