[Potentiation of NO-dependent activation of soluble guanylyl cyclase by 5-nitroisatin and antiviral preparatation arbidol]

Biomed Khim. 2013 May-Jun;59(3):295-304. doi: 10.18097/pbmc20135903295.
[Article in Russian]

Abstract

Isatin (indole-dione) is an endogenous indole that exibits a wide range of biological and physiological activity. The influence of isatin derivatives 5-nitroisatin and arbidol (an antiviral preparatation) on spermine NONO-induced activation of human platelet soluble guanylyl cyclase was investigated. 5-nitroistnin and arbidol had no effect on basal activity, but synergistically increased in a concentration-dependent manner the spermine NONO-induced activation of this enzyme. 5-Nitroisatin and arbidol, like YC-1, sensitized guanylyl cyclase towards nitric oxide (NO) and produced a leftward shift of the spermine NONO concentration response curve. At the same time both compounds used did not influence the activation of guanylyl cyclase by YC-1 and did not change the synergistic increase of spermine NONO-induced activation of soluble guanylyl cyclase in the presence of YC-1. This suggests that 5-nitroisanin and arbidol did not compete with YC-1. Addition of isatin did not change the synergistic increase in the spermine NONO-induced guanylyl cyclase activation by 5-nitroisatin and arbidol and did not influence a leftward shift of spermine NONO concentration response curve produced by these compounds. These data suggest lack of competitive interaction between isatin and both its derivatives used.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / pharmacology*
  • Blood Platelets / enzymology*
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Female
  • Guanylate Cyclase / metabolism*
  • Humans
  • Indoles / pharmacology*
  • Isatin / analogs & derivatives*
  • Isatin / pharmacology*
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Soluble Guanylyl Cyclase
  • Spermine / pharmacology

Substances

  • Antiviral Agents
  • Indoles
  • Receptors, Cytoplasmic and Nuclear
  • Spermine
  • Nitric Oxide
  • Isatin
  • umifenovir
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase