title: [Inhibition of no-dependent soluble human platelet guanylate cyclase by isatin].
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.
authors.forename: I S
authors.initials: IS
authors.lastname: Severina
authors.forename: A Iu
authors.initials: AIu
authors.lastname: Shchegolev
authors.forename: G V
authors.initials: GV
authors.lastname: Ponomarev
authors.forename: A E
authors.initials: AE
authors.lastname: Medvedev
mesh_terms: D000328:Adult; D000494:Allosteric Regulation / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology / Q000201:enzymology*; D020536:Enzyme Activators / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006801:Humans; D007191:Indazoles / Q000494:pharmacology; D007510:Isatin / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D020536:Enzyme Activators; D005663:Furans; D007191:Indazoles; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D009569:Nitric Oxide; D006418:Heme; D007510:Isatin; D006162:Guanylate Cyclase