Effect of nitroso complexes of some transition metals on the activity of soluble guanylate cyclase.
Effects of nitroso complexes of some transition metals (Fe, Co, Cr), differing in the character of NO oxidation on the activity of human and rat platelet guanylate cyclase were studied. 3 types of nitroso complexes were used: (1) NO group carries a positive charge--a nitrosonium cation (Na2[FeNO + (CN)5]-nitroprusside); (2) NO is neutral--(K3[CrNO(CN)5 and [CoNO(NH3)5]SO4) and (3) NO is coordinated as anion NO- (K3[CoNO-(CN)5]. It is shown that the highest stimulatory effect is produced by sodium nitroprusside, whose activating action is due to the interaction of its NO group with the guanylate cyclase heme. Nitroso complexes (Co and Cr) the NO group of which is neutral stimulated guanylate cyclase activity insignificantly and this activation was not guanylate cyclase heme directed. Nitroso complex (Co) with NO coordinated as anion NO(-)--is a guanylate cyclase inhibitor. In contrast to nitroprusside, the nitroso complexes used (Co and Cr) have no hypotensive effect. It was concluded that the essential requirement for the realization of the hypotensive effect of transition metals' nitroso complexes is the ability of these compounds to activate soluble guanylate cyclase solely by the heme-dependent mechanism.
Institute of Biological and Medical Chemistry, Academy of Medical Sciences, Moscow, Russia.
I S
IS
Severina
O G
OG
Bussygina
N B
NB
Grigorjev
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D002336:Carnosine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000097:blood / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008670:Metals / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology*; D051381:Rats; D012995:Solubility
D008670:Metals; D009603:Nitroso Compounds; D009599:Nitroprusside; D002336:Carnosine; D006162:Guanylate Cyclase