Nitric oxide. Potentiation of NO-dependent activation of soluble guanylate cyclase: (Patho)physiological and pharmacotherapeutic importance

The paper reviews the molecular mechanism underlying the physiological effects of nitric oxide (NO), the role of the signalling system: NO-soluble guanylate cyclase-cyclic 3',5'-guanosine monophosphate (cGMP) in the realization of NO action. The data concerning the basic chemical characteristics of guanylate cyclase, such as the subunits structure, isoforms, modem concepts of the catalytic and regulatory centers of the enzyme are presented. The role of guanylate cyclase heme and the enzyme itself in the realization of physiological effects of NO is demonstrated. The data concerning a new NO-independent, allosteric activator of soluble guanylate cyclase, YC-1 (benzyl indasol derivative) synergistically increased the NO-dependent activation of soluble guanylate cyclase are presented. The data on guanylate cyclase sites responsible for binding of the enzyme with YC-1 and possible molecular mechanism underlying the synergistic increase of NO-dependent activation of soluble guanylate cyclase by YC-1 are presented. New compounds of endogenous nature capable to potentiate and synergistically increase the activation of guanylate cyclase by NO-donors have been revealed and investigated. The important physiological, pharmacotherapeutical and pathophysiological significance of this new fact is discussed.