2Department of Bioorganic Chemistry, School of Biology, Lomonosov Moscow State University, Moscow, 119899 Russia
3Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky pr. 37, Moscow, 117913 Russia
* To whom correspondence should be addressed.
Received May 13, 1999; Revision received July 9, 1999
The ability of benzodifuroxan (BDF) to activate human platelet guanylate cyclase was investigated. The maximal stimulatory effect (1160 ± 86%) was observed at 0.01 mM concentration. Sodium nitroprusside produced the same stimulatory effect (1220 ± 100%) but at a higher concentration (0.1 mM). 1-H-[1,2,4,]-Oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), an inhibitor of NO-dependent guanylate cyclase activation, attenuated the stimulatory effect of BDF (0.01 mM) by 75% and that of sodium nitroprusside (0.1 mM) by 80%. Increasing dithiothreitol concentration in the sample from 2.10-6 to 2.10-4 M increased the stimulatory effect of BDF 2.7-fold. The possible involvement of sulfhydryl groups of low-molecular-weight thiols and guanylate cyclase in thiol-dependent activation of the enzyme is discussed. We have also found that BDF is a highly effective inhibitor of ADP-induced human platelet aggregation with IC50 of 6·10-8 M. The effect of sodium nitroprusside was much weaker (IC50, 5·10-5 M).
KEY WORDS: soluble guanylate cyclase, nitric oxide, benzodifuroxan, platelet aggregation