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

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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 μM) 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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Authors and Affiliations

  1. Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, ul. Pogodinskaya 10, Moscow, 119121, Russia

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

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  1. I. S. Severina
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  2. A. Yu. Schegolev
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  3. G. V. Ponomarev
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  4. A. E. Medvedev
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Correspondence to A. E. Medvedev.

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Original Russian Text © I.S. Severina, A.Yu. Schegolev, G.V. Ponomarev, A.E. Medvedev, 2011, published in Biomeditsinskaya Khimiya.

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Severina, I.S., Schegolev, A.Y., Ponomarev, G.V. et al. Inhibition of NO-dependent soluble human platelet guanylate cyclase by isatin. Biochem. Moscow Suppl. Ser. B 5, 263–267 (2011). https://doi.org/10.1134/S1990750811030115

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  • DOI: https://doi.org/10.1134/S1990750811030115

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