A new activator of soluble guanylate cyclase generated by nitric oxide and having antihypertensive and anti-aggregation properties
Busygina, O.G.; Belushkina, N.N.; Grigor'ev, N.B.; Severina, I.S.
Biokhimiia 60(9): 1460-1467
1995
ISSN/ISBN: 0320-9725 PMID: 8562654 Document Number: 445277
The effects of aminoethylisothiuronium bromide known as a radioprotector on the activity of human platelet soluble guanylate cyclase and on ADP-induced aggregation of human platelets have been studied. It has been shown that in Tris-buffer and at definite pH values aminoethylisothiuronium bromide is converted into mercaptoethylguanidine as a result of a transguanidine rearrangement. The latter contains in its molecule both guanidine and SH-groups which appear to be the donor and acceptor of nitric oxide, respectively. It was found that after its rearrangement into mercaptoethylguanidine, aminoethylisothiuronium bromide activates human platelet soluble guanylate cyclase, inhibits ADP-induced aggregation of human platelets and accelerates their spontaneous disaggregation. The stimulating effect of aminoethylisothiuronium bromide depends on the effectiveness of its transguanidine rearrangement into mercaptoethylguanidine. A molecular mechanism of the hypotensive side effect of aminoethylisothiuronium bromide is proposed.