Advertisement

Einfluß von Thiolen auf die subzelluläre Wirkungsvermittlung der organischen Nitrate

  • H. Schröder
  • E. Noack

Zusammenfassung

Organische Nitrate wirken auf subzellulärer Ebene über eine Stimulierung des Enzyms Guanylzyklase (E.C. 4.6.1.2) [1, 9]. Dieses Enzym ist verantwortlich für die Bildung von cGMP (zyklisches Guanosin-3′:5′-monophosphat) aus GTP (Guano-sin-5′-triphosphat). Das gebildete cGMP relaxiert konzentrationsabhängig über noch unbekannte Zwischenschritte die glatte Gefäßmuskulatur und vermittelt so die hämodynamische Wirkung der organischen Nitrate.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. 1.
    Böhme E, Graf G, Schultz G (1978) Effects of sodium nitroprusside and other smooth muscle relaxants on cyclic GMP formation in smooth muscle and platelets. Adv Cyclic Nucleotide Res 9: 131–143PubMedGoogle Scholar
  2. 2.
    Craven PA, DeRubertis FR (1983) Requirements for heme in the activation of purified guanylate cyclase by nitric oxide. Biochim Biophys Acta 745: 310–321PubMedCrossRefGoogle Scholar
  3. 3.
    Gruetter CA, Kadowitz PJ, Ingnarro LJ (1981) Methylene blue inhibits coronary arterial relaxation and guanylate cyclase activation by nitroglycerin, sodium nitrite, and amyl nitrite. Can J Physiol Pharmacol 59: 150–156PubMedCrossRefGoogle Scholar
  4. 4.
    Horowitz JD, Antman EM, Lorell BH, Barry WH, Smith TW (1983) Potentiation of the cardiovascular effects of nitroglycerin by N-acetylcysteine. Circulation 68: 1247–1253PubMedCrossRefGoogle Scholar
  5. 5.
    Ignarro LJ, Gruetter CA (1980) Requirement of thiols for activation of coronary arterial guanylate cyclase by glyceryl trinitrate and sodium nitrite - possible involvement of S-nitrosothiols. Biochim Biophys Acta 631: 221–231PubMedCrossRefGoogle Scholar
  6. 6.
    Ignarro LJ, Kadowitz PJ, Baricos WH (1981) Evidence that regulation of hepatic guanylate cyclase activity involves interactions between catalytic site - SH groups and both substrate and activator. Arch Biochem Biophys 208: 75–86PubMedCrossRefGoogle Scholar
  7. 7.
    Ignarro LJ, Lippton H, Edward JC, Baricos WH, Hyman AL, Kadowitz PJ, Gruetter CA (1981) Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: Evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther 218: 739–749PubMedGoogle Scholar
  8. 8.
    Kimura H, Mittal CK, Murad F (1975) Activation of guanylate cyclase from rat liver and other tissues by sodium azide. J Biol Chem 250: 8016–8022PubMedGoogle Scholar
  9. 9.
    Kukovetz WR, Holzmann S, Wurm A, Pöch G (1979) Evidence for cyclic GMP-mediated relaxant effects of nitrocompounds in coronary smooth muscle. Naunyn-Schmiedebergs Arch Pharmacol 310: 129–138PubMedCrossRefGoogle Scholar
  10. 10.
    Laustiola K, Vuorinen P, Vapaatalo H, Metsä-Ketelä T (1983) Effects of cysteine and nitroglycerine on bovine heart guanylate cyclase and on tissue cyclic GMP and lactate of rat atria. Eur J Pharmacol 91: 301–304PubMedCrossRefGoogle Scholar
  11. 11.
    Noack E, Bonn R, Sandrock K (1983) Beziehungen zwischen chemisch-physikalischen und vaso- dilatatorischen Eigenschaften organischer Nitrate als Anhalt für ihre Wirksamkeit und Wirkdauer. In: Köhler E, Noack E, Schrey A, Weiß M (Hrsg) Mononitrat. 2. Workshop Kronberg, Febr. 1983. Wolf, München, S 13–20Google Scholar
  12. 12.
    Noack E, Schröder H (1984) Differences between the guanylate cyclase stimulatory and vaso- dilatory potency of organic nitrates. Naunyn-Schmiedebergs Arch Pharmacol 325: R1 (Abstract 2)CrossRefGoogle Scholar
  13. 13.
    Schröder H, Noack E, Müller R (1985) Evidence for a correlation between nitric oxide formation by cleavage of organic nitrates and activation of the guanylate cyclase. J Molec Cell Cardiol 17: 931–934CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • H. Schröder
    • 1
  • E. Noack
  1. 1.Pharmakologisches Institut der UniversitätDüsseldorf 1Germany

Personalised recommendations