Activators of soluble guanylate cyclase for the treatment of male erectile dysfunction
Activators of soluble guanylate cyclase for the treatment of male erectile dysfunction
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DOI：
10.1038/sj.ijir.3900801
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发表时间：
2002-02-01
影响因子：
2.6
通讯作者：
Sullivan, JP
中科院分区：
文献类型：
--
作者：
Brioni, JD;Nakane, M;Sullivan, JP
可溶性鸟苷酸环化酶(sGC)是海绵体平滑肌细胞中的重要酶，是cGMP合成的调节因子之一。西地那非（Viagra TM ）在治疗男性勃起功能障碍中的功效表明了cGMP系统在勃起反应中的重要性，因为cGMP水平的增加导致海绵体松弛。 sGC 在性刺激过程中被一氧化氮 (NO) 生理激活，并且其活性可以通过多种 NO 供体在药理学上增强。 YC-1 等药物在与酶中的新变构位点（与 NO 结合位点不同的位点）结合后也可以激活 sGC。 YC-1可以松弛家兔海绵体组织，促进体内阴茎勃起。本综述总结了这种新型变构位点的酶学、生物化学和药理学及其与阴茎功能调节的相关性。这种类型的 sGC 激活剂代表了一类新型化合物，与经典的 NO 供体相比具有不同的药理学特征，它们可能有益于治疗男性勃起功能障碍。
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(TM)) 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.