YC-1-Like Potentiation of NO-Dependent Activation of Soluble Guanylate Cyclase by Derivatives of Protoporphyrin IX

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I. S. Severina^*, N. V. Pyatakova, A. Yu. Shchegolev, and G. V. Ponomarev

Orechovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya ul. 10, 119121 Moscow, Russia; fax: (7-495) 245-0857; E-mail: irina.severina@ibmc.msk.ru

^* To whom correspondence should be addressed.

Received May 12, 2005

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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 µM sodium nitroprusside and 5 µM dimegin (or 5 µM HP) was 190 ± 19 and 134 ± 10%, respectively. The synergistic activation of guanylate cyclase by 3 µM YC-1 and 10 µM 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 µM) and sodium nitroprusside (10 µM) 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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KEY WORDS: soluble guanylate cyclase, nitric oxide, derivatives of protoporphyrin IX: 2,4-di(1-methoxyethyl)-deuteroporphyrin IX disodium salt and hematoporphyrin IX

DOI: 10.1134/S0006297906030163

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