Inhibition of ADP-induced platelet aggregation by guanidine thiols--a novel class of guanylate cyclase activators and NO-synthase substrates
Belushkina, N.N.; Severina, I.S.
Biokhimiia 61(12): 2140-2146
1996
ISSN/ISBN: 0320-9725 PMID: 9156556 Document Number: 458275
Antiaggregatory properties of guanidine thiol derivatives and their effect on human platelet guanylate cyclase activity were studied. The molecules of guanidine thiols contain guanidine and thiol groups which are the donor and acceptor of nitric oxide (NO), respectively. Three synthetic guanidine thiol derivatives were studied including mercaptoethylguanidine (MEG), mercaptoethylguanidine disulfide (MEG-disulfide), and mercaptoethylguanidine methylated at SH-group (S-methylmercaptoethylguanidine (S-methyl MEG)). All compounds are the substrates of NO-synthase and activators of human platelet guanylate cyclase. The stimulatory effects of MEG and MEG-disulfide on guanylate cyclase activity were 2- and 4-fold higher, respectively, than the effect of L-arginine. Stimulation of the enzyme by S-methyl MEG is similar to L-arginine. Antiaggregatory properties of these compounds correspond to the extent of guanylate cyclase activation. Extent of guanylate cyclase activation (S-methyl MEG < MEG < MEG-disulfide) significantly correlates with inhibition of ADP-induced platelet aggregation and with acceleration of spontaneous disaggregation of platelets. The mechanism of directed enhancement of antiaggregatory properties of the compounds can depend on their chemical structure and extent of guanylate cyclase activation.