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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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ISSN
1437-4331
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Volume 41, Issue 7

Issues

Soluble Guanylyl Cyclase: Physiological Role as an NO Receptor and the Potential Molecular Target for Therapeutic Application

Masaki Nakane
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/CCLM.2003.131

Abstract

Nitric oxide (NO) activates soluble guanylyl cyclase, which results in an increased synthesis of cyclic guanosine 3′,5′-cyclic monophosphate (cGMP), smooth muscle relaxation and vasodilation. The heme group in soluble guanylyl cyclase binds NO and allosterically activates the catalytic site. In addition, a second allosteric site that synergistically activates the enzyme has been reported. BAY 41-2272 was reported as an NO-independent activator of soluble guanylyl cyclase. Treatment with this compound results in anti-platelet activity, a decrease in blood pressure and an increase in survival, indicating a potential for treating cardiovascular diseases. YC-1, another NO-independent activator, activates soluble guanylyl cyclase and the activity is enhanced in the presence of NO. YC-1 relaxed tissue strips in organ bath. Consistent with its biochemical activity, YC-1 induced penile erection in a conscious rat model. Recently, we found a novel series of soluble guanylyl cyclase activators that also NO-independently activate soluble guanylyl cyclase and cause penile erection, suggesting a synergy with the endogenous NO production in vivo. Here I review the NO/cGMP signal transduction pathway and define soluble guanylyl cyclase modulators as a novel approach for the treatment of cardiovascular diseases and erectile dysfunction.

About the article

Published Online: 2005-06-01

Published in Print: 2003-07-21


Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 41, Issue 7, Pages 865–870, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2003.131.

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