[Soluble forms of guanylate cyclases: mechanism of activation by nitrogen oxide and role in platelet aggregation].
The paper gives data on the role of heme in the functioning soluble forms of guanylate cyclase (of human platelets, rat heart and platelets), on the mechanism of nitrogen oxide-induced heme-dependent activation of enzymes, on the role of platelet guanylate cyclase in the regulation of human platelet aggregation/disaggregation and on the mechanism of antihypertensive and antiaggregatory action of enzyme activators. The instability of relationships of the protein molecule of human platelet guanylate cyclase and heme (regarded as a prosthetic group of the enzyme) results in heme loss during purification of the enzyme and preparation of a heme-deficient agent having a drastically reduced ability to sodium nitroprusside activation. Soluble rat platelet guanylate cyclase was found to be present in these cell originally in a heme-deficient form, it was not activated by sodium nitroprusside and, unlike the routine concepts, heme is not a moiety of this enzyme molecule. The water soluble antioxidant carnosine (beta-alanyl-L-histidine) inhibits sodium nitroprusside activation of guanylate cyclase by interacting with the heme of enzyme of the NO group of nitroprusside and may be useful to reveal the degree of htmt saturation of guanylate cyclase. The study of the mechanism of activation of guanylate cyclase by nitroso complexes of transition metals (Fe, Cr, Co) showed that their realization of antihypertensive effects required only heme-dependent activation of the enzyme. ADF-induced aggregation of human (donor) platelets is followed by stimulation of guanylate cyclase by various activators (despite heme involvement in the mechanism of activation) with concurrent elevations of platelet cGMP levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Severina
I S
IS
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D002336:Carnosine / Q000494:pharmacology; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000187:drug effects / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide; D009599:Nitroprusside / Q000494:pharmacology; D010974:Platelet Aggregation; D051381:Rats; D012995:Solubility
D009599:Nitroprusside; D009569:Nitric Oxide; D006418:Heme; D002336:Carnosine; D006162:Guanylate Cyclase
Rastvorimye formy guanilattsiklaz. Mekhanizm aktivatsii oksidom azota, rol' v agregatsii trombotsitov.