Inhibition of NO-dependent soluble human platelet guanylate cyclase by isatin |
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Authors: | I S Severina A Yu Schegolev G V Ponomarev A E Medvedev |
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Institution: | 1.Institute of Biomedical Chemistry,Russian Academy of Medical Sciences,Moscow,Russia |
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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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