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

Severina I.S.1, Schegolev A.Yu.1, Ponomarev G.V.1, Medvedev A.E.1

1. Institute of Biomedical Chemistry, Russian Academy of Medical Sciences
Section: Experimental/Clinical Study
DOI: 10.18097/PBMC20115703300      PubMed Id: 21863743
Year: 2011  Volume: 57  Issue: 3  Pages: 300-307
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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Keywords: guanylate cyclase, nitric oxide (NO), isatin

Severina, I. S., Schegolev, A. Yu., Ponomarev, G. V., Medvedev, A. E. (2011). Inhibition of NO-dependent soluble human platelet guanylate cyclase by isatin. Biomeditsinskaya Khimiya, 57(3), 300-307.
This paper is also available as the English translation: 10.1134/S1990750811030115
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