2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Inhibition of nitric oxide synthesis by methylene blue

      , ,
      Biochemical Pharmacology
      Elsevier BV

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Methylene blue appears to inhibit nitric oxide-stimulated soluble guanylyl cyclase and has been widely used for inhibition of cGMP-mediated processes. We report here that endothelium-dependent relaxation of isolated blood vessels and NO synthase-dependent cGMP formation in cultured endothelial cells were both markedly more sensitive to inhibition by methylene blue than effects induced by direct activation of soluble guanylyl cyclase. These discrepancies were also observed when superoxide dismutase (SOD) was present to protect NO from inactivation by superoxide anion. Subsequent experiments showed that formation of L-citrulline by purified NO synthase was completely inhibited by 30 microM methylene blue (IC50 = 5.3 and 9.2 microM in the absence and presence of SOD, respectively), whereas guanylyl cyclase stimulated by S-nitrosoglutathione was far less sensitive to the drug (50% inhibition at approximately 60 microM, and maximal inhibition of 72% at 1 mM methylene blue). Experimental evidence indicated that oxidation of NADPH, tetrahydrobiopterin or reduced flavins does not account for the inhibitory effects of methylene blue. Our data suggest that methylene blue acts as a direct inhibitor of NO synthase and is a much less specific and potent inhibitor of guanylyl cyclase than hitherto assumed.

          Related collections

          Author and article information

          Journal
          Biochemical Pharmacology
          Biochemical Pharmacology
          Elsevier BV
          00062952
          January 1993
          January 1993
          : 45
          : 2
          : 367-374
          Article
          10.1016/0006-2952(93)90072-5
          7679577
          c5c77c52-42de-488a-8436-56b505ba53b9
          © 1993

          https://www.elsevier.com/tdm/userlicense/1.0/

          History

          Comments

          Comment on this article