Severina I S
Biomed Khim. 2007 Jul-Aug;53(4):385-99.
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.
本文综述了一氧化氮（NO）生理效应的分子机制，以及信号系统：NO-可溶性鸟苷酸环化酶-环3',5'-鸟苷单磷酸（cGMP）在NO作用实现中的作用。文中介绍了关于鸟苷酸环化酶基本化学特性的数据，如亚基结构、同工型、该酶催化和调节中心的现代概念。证明了鸟苷酸环化酶血红素和酶本身在NO生理效应实现中的作用。文中介绍了一种新的不依赖NO的可溶性鸟苷酸环化酶变构激活剂YC-1（苄基吲唑衍生物）协同增强NO依赖的可溶性鸟苷酸环化酶激活作用的数据。文中给出了负责鸟苷酸环化酶与YC-1结合的位点数据，以及YC-1协同增强NO依赖的可溶性鸟苷酸环化酶激活作用的可能分子机制。已发现并研究了能够增强并协同增加NO供体对鸟苷酸环化酶激活作用的内源性新化合物。讨论了这一新发现的重要生理、药物治疗和病理生理意义。
