Guanidine thiol--a new activator of soluble guanylate cyclase with antihypertensive and antiaggregatory properties.
Effects of aminoethylisothiuronium bromide (AET), known as radioprotector, on human platelet soluble guanylate cyclase and on ADP-induced human platelets aggregation were studied. It was shown that AET - in Tris buffer and at certain pH values - is converted, via transguanidine rearrangement, to mercaptoethylguanidine. The latter contains in its molecule both the guanidine and SH groups which act as donor and acceptor of nitric oxide (NO), respectively. It was demonstrated that AET, after its rearrangement to mercaptoethylguanidine, is able to activate human platelet soluble guanylate cyclase, as well as to inhibit ADP-induced human stimulatory effect of AET is dependent on the effectiveness of its transguanidine rearrangement to mercaptoethylguanidine. The molecular mechanism of the hypotensive by - effect of AET is proposed.
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, Russia.
I S
IS
Severina
O G
OG
Bussygina
N N
NN
Belushkina
N B
NB
Grigoryev
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D004789:Enzyme Activation; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D000338:beta-Aminoethyl Isothiourea / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000959:Antihypertensive Agents; D006146:Guanidines; D010975:Platelet Aggregation Inhibitors; D000338:beta-Aminoethyl Isothiourea; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D001120:Arginine; D006162:Guanylate Cyclase; C100078:2-mercaptoethylguanidine