Brioni J D, Nakane M, Hsieh G C, Moreland R B, Kolasa T, Sullivan J P
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Int J Impot Res. 2002 Feb;14(1):8-14. doi: 10.1038/sj.ijir.3900801.
Soluble guanylate cyclase (sGC) is an important enzyme in corpus cavernosum smooth muscle cells as it is one of the regulators of the synthesis of cGMP. The efficacy of sildenafil (Viagra) in the treatment of male erectile dysfunction indicates the importance of the cGMP system in the erectile response as the increased levels of cGMP induce relaxation of the corpus cavernosum. sGC is physiologically activated by nitric oxide (NO) during sexual stimulation, and its activity can be pharmacologically enhanced by several NO-donors. Agents like YC-1 can also activate sGC after binding to a novel allosteric site in the enzyme, a site different from the NO binding site. YC-1 can relax rabbit cavernosal tissue and it facilitates penile erection in vivo. This review summarizes the enzymology, biochemistry and pharmacology of this novel allosteric site and its relevance for the regulation of penile function. This type of sGC activators represent a new class of compounds with a different pharmacological profile in comparison to the classical NO-donors and they could be beneficial for the treatment of male erectile dysfunction.
可溶性鸟苷酸环化酶（sGC）是海绵体平滑肌细胞中的一种重要酶，因为它是cGMP合成的调节因子之一。西地那非（伟哥）治疗男性勃起功能障碍的疗效表明cGMP系统在勃起反应中的重要性，因为cGMP水平升高会导致海绵体松弛。在性刺激过程中，sGC在生理上由一氧化氮（NO）激活，其活性可通过几种NO供体在药理学上增强。像YC-1这样的药物在与该酶中的一个新的变构位点结合后也可以激活sGC，该位点不同于NO结合位点。YC-1可以使兔海绵体组织松弛，并在体内促进阴茎勃起。这篇综述总结了这个新变构位点的酶学、生物化学和药理学及其与阴茎功能调节的相关性。与经典的NO供体相比，这种类型的sGC激活剂代表了一类具有不同药理学特征的新化合物，它们可能对治疗男性勃起功能障碍有益。
