Role of Soluble Guanylate Cyclase in Reactivation of Choline Esterase Inhibited by Phosphoorganic Compounds

N. V. Pyatakova¹, N. B. Grigoryev², and I. S. Severina^1*

¹Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya ul. 10, Moscow, 119832 Russia; fax: (095) 245-0857

²State Research Center NIOPIK, Bolshaya Sadovaya ul. 1, Moscow, 103787 Russia; fax: (095) 292-6511

^* To whom correspondence should be addressed.

Received March 27, 1998; Revision received September 29, 1998

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The effects of possible activators of soluble guanylate cyclase were studied. Hydroxylamine and some oxime derivatives such as pyridinium aldoximes and bispyridinium dioxime (dipyroxime) were tested as possible guanylate cyclase activators. These compounds are known to be reactivators of choline esterase which has been preinhibited with phosphoorganic compounds. All the tested compounds were found to activate human platelet guanylate cyclase in the concentration range 10^-6-10^-3 M. The highest stimulatory affect 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 electrochemical (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 their biotransformation. The possible role of guanylate cyclase activation by oxime derivatives in the mechanism underlying the reactivation of inhibited choline esterase at the cell level is discussed.

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KEY WORDS: guanylate cyclase, nitric oxide, oximes, choline esterase reactivators

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