[A new activator of soluble guanylate cyclase generated by nitric oxide and having antihypertensive and anti-aggregation properties].
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.
Busygina
O G
OG
Belushkina
N N
NN
Grigor'ev
N B
NB
Severina
I S
IS
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012995:Solubility; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology*
D000959:Antihypertensive Agents; D010975:Platelet Aggregation Inhibitors; D000338:beta-Aminoethyl Isothiourea; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D006162:Guanylate Cyclase
Novyĭ aktivator rastvorimoĭ guanilattsiklazy, generiruiushchiĭ oksid azota i obladaiushchiĭ antigipertenzivnym i antiagregatsionnym svoĭstvami.