Inhibition of NO-dependent soluble human platelet guanylate cyclase by isatin


1. Institute of Biomedical Chemistry, Russian Academy of Medical Sciences
Type: Experimental/clinical study
DOI: 10.18097/pbmc20115703300      UDK: 616.155.16.615.9      PubMed Id: 21863743
Year: 2011 vol: 57  issue:3  pages: 300-307
Abstract: Isatin (indole-dione-2,3) is an endogenous indole that exhibits a wide spectrum of biological and pharmacological activities. Physiologically relevant concentrations of isatin (ranged from 1 nM to 10 M) did not influence basal activity of soluble human platelet guanylate cyclase (sGC), but caused a bell-shaped inhibition of the NO-activated enzyme. Inhibition of the NO-dependent activation by isatin did not depend on a chemical nature of the NO donors. The inhibitory effects of ODC (a heme-dependent inhibitor of sGC) and isatin were non-additive suggesting that the inhibitory effect of isatin may involve the heme binding domain (possibly heme iron) and experiments with hemin revealed some isatin-dependent changes in its spectrum. Isatin also inhibited sGC activation by the allosteric activator YC-1. It is suggested that the bell shaped inhibition of the NO-dependent activation of sGC by isatin may be attributed to complex interaction of isatin with the heme binding domain and the allosteric YC-1-binding site of sGC.
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Reference: Severina I.S., Schegolev A.Yu., Ponomarev G.V., Medvedev A.E., Inhibition of NO-dependent soluble human platelet guanylate cyclase by isatin, Biomeditsinskaya khimiya, 2011, vol: 57(3), 300-307.
This paper is also available as the English translation:10.1134/S1990750811030115