Nitric Oxide. Potentiation of NO-Dependent Activation of Soluble Guanylate Cyclase: (Patho)physiological and Pharmacotherapeutic Importance

摘要

The review highlights the molecular mechanism underlying the physiological effects of nitric oxide(NO), the role of signaling system: NO-soluble guanylate cyclase–cyclic 3',5'-guanosine monophosphate(cGMP) in the realization of NO action. This review considers data on basic chemical characteristics of guany-late cyclase, such as the subunits structure, isoforms, modern concepts of the catalytic and regulatory centersof this enzyme. Realization of physiological effects of NO by guanylate cyclase depends on its heme prosteticgroup. NO-dependent activation of guanylate cyclase may be synergistically increased by a new NO- indepen-dent, allosteric activator of soluble guanylate cyclase–YC-1–(benzyl indasol derivative). Special attention ispaid to the data on guanylate cyclase sites responcible for binding of the enzyme with YC-1 and the possiblemolecular mechanism underlying the synergistic increase of NO-dependent activation of soluble guanylatecyclase by YC-1. New compounds of endogenous nature capable to potentiate and synergistically increase theactivation of guanylate cyclase by NO-donors have been found and investigated. The important physiological,pharmacotherapeutical and pathophysiological significance of this new fact is discussed.