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.
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.
Severina I.S. et al. Inhibition of NO-dependent soluble human platelet guanylate cyclase by isatin // Biomeditsinskaya Khimiya. - 2011. - V. 57. -N 3. - P. 300-307.
Severina I.S. et al., "Inhibition of NO-dependent soluble human platelet guanylate cyclase by isatin." Biomeditsinskaya Khimiya 57.3 (2011): 300-307.
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.
