Soluble Guanylyl Cyclase: Physiological Role as an NO Receptor and the Potential Molecular Target for Therapeutic Application
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Masaki Nakane
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.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- 18th ICCC 2002 Kyoto
- Essential Hypertension: Genes and Dreams
- Alteration of Nucleotide Metabolism: A New Mechanism for Mitochondrial Disorders
- Tryptophan Metabolites and Brain Disorders
- The Role of Interleukin-4 and Interleukin-13 in the Non-Immunologic Aspects of Asthma Pathogenesis
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- The Increasing Impact of Laboratory Medicine on Clinical Cardiology
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- Polymorphisms in the IL-4 and IL-4R [α] Genes and Allergic Asthma
- Circulating Transforming Growth Factor-β1, Lipoprotein(a) and Cellular Adhesion Molecules in Angiographically Assessed Coronary Artery Disease
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- Clinical Evaluation of Nine Free Thyroxine Assays: Persistent Problems in Particular Populations
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