[The role of SH-groups in guanidine thiols--new substrates for NO-synthase--in stimulating the activity of guanylate cyclase].

O G Busygina, N B Grigor'ev, I S Severina

Index: Biokhimiia 61(1) , 119-25, (1996)

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Abstract

Guanidine thiol derivatives--a new class of soluble guanylate cyclase activators--have been studied. Guanidine thiols contain in their molecule both the guanidine and thiol groups which act as donors acceptors of nitric oxide (NO), respectively. The role of the guanidine thiol SH-groups in the mechanism of soluble guanylate cyclase activation has been evaluated. The effect of three guanidine thiol derivatives: mercaptoethylguanidine (MEG), mercaptoethylguanidine disulfide (MEG disulfide) and S-methyl mercaptoethylguanidine (S-methyl MEG) on human platelet guanylate cyclase activity, has been examined. It was found that all the compounds tested in this study were substrates for NO-synthase and guanylate cyclase activators. The stimulatory effects of MEG and MEG disulfide surpassed the L-arginine-induced activation of guanylate cyclase-2- and 4-fold, respectively. The enzyme stimulation by S-methyl MEG was of the same order as that of L-arginine. The important role of S-acceptor groups of guanidine thiols in the mechanism of directed increase of guanylate cyclase activation was established. This mechanism explains the nature of differences in the intensity of guanylate cyclase activation by the guanidine thiols under study. The NO-acceptor properties of disulfide bond of guanidine thiols in the case of the NO-synthase mechanism of NO formation have been established.