The influence of protoporphyrin IX derivatives--2,4-di(1-methoxyethyl)-deuteroporphyrin IX disodium salt (dimegin) and hematoporphyrin IX (HP)--on the activation of human platelet soluble guanylate cyclase by sodium nitroprusside was investigated. Dimegin and HP, like 1-benzyl-3-(hydroxymethyl-2-furyl)indazole (YC-1), produce synergistic effects on the activation of soluble guanylate cyclase by sodium nitroprusside. The synergistic activation of the enzyme by the combination of 10 microM sodium nitroprusside and 5 microM dimegin (or 5 microM HP) was 190 +/- 19 and 134 +/- 10%, respectively. The synergistic activation of guanylate cyclase by 3 microM YC-1 and 10 microM sodium nitroprusside was 255 +/- 19%. Dimegin and HP had no effect on the activation of guanylate cyclase by YC-1; they did not change the synergistic effect of YC-1 (3 microM) and sodium nitroprusside (10 microM) on guanylate cyclase activity. The synergistic activation of NO-stimulated guanylate cyclase activity by dimegin and HP represents a new biochemical effect of these compounds that may have important pharmacotherapeutic and physiological significance.
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