Role of soluble guanylate cyclase in reactivation of choline esterase inhibited by phosphoorganic compounds

The effects of possible activators of soluble guanylate cyclase were studie d. Hydroxylamine and some oxime derivatives such as pyridinium aldoximes an d bispyridinium dioxime (dipyroxime) were tested as possible guanylate cycl ase activators. These compounds are known to be reactivators of choline est erase which has been preinhibited with phosphoorganic compounds. All the te sted compounds were found to activate human platelet guanylate cyclase in t he concentration range 10(-6)-10(-3) M. The highest stimulatory effect was achieved at 10(-4) M with hydroxylamine and dipyroxime: 210 +/- 10 and 320 +/- 15%, respectively. Potassium ferricyanide oxidation of these compounds under mild conditions formed nitroprusside ion, as registered by the electr ochemical (polarographic) method; this is evidence that these compounds are NO donors. It is concluded that the activation of guanylate cyclase by the tested compounds is associated with their ability to generate NO during th eir biotransformation. The possible role of guanylate cyclase activation by oxime derivatives in the mechanism underlying the reactivation of inhibite d choline esterase at the cell level is discussed.