Molecular pharmacotherapeutic targeting of PDE5 for preservation of penile health
Molecular pharmacotherapeutic targeting of PDE5 for preservation of penile health
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DOI：
10.2164/jandrol.107.003483
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发表时间：
2008-01-01
影响因子：
--
通讯作者：
Burnett, Arthur L.
中科院分区：
文献类型：
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作者：
Burnett, Arthur L.
勃起生理学的分子科学已经确定磷酸二酯酶5（PDE 5）在阴茎中起重要的生物学作用。目前该领域的研究已经揭示了这种分子效应物与阴茎勃起相关，通过降解勃起介导的一氧化氮（NO）信号传导途径的第二信使产物3 '，5'-环鸟苷一磷酸来控制勃起反应。因此，PDE 5已被靶向用于性医学目的，并且口服施用的PDE 5抑制剂如西地那非、他达拉非和伐地那非构成勃起功能障碍（艾德）的首要干预。对阴茎中PDE 5调节的新研究表明了酶的替代作用和涉及其分子相互作用的新治疗机会。特别是，在雄激素缺乏、NO生物活性降低和氧化应激相关的炎症变化的紊乱下，PDE 5功能改变，从而导致各种勃起障碍，包括性腺功能减退相关的艾德、复发性缺血性阴茎异常勃起、阴茎血管病变和阴茎纤维化。这篇综述对PDE 5调节系统在阴茎中的多方面作用及其与应用现有和新兴的勃起障碍治疗策略的相关性进行了严格的检查。
The molecular science of erection physiology has established that phosphodiesterase 5 (PDE5) serves an important biological role in the penis. Current research in the field has revealed this molecular effector to be relevant for penile erection, controlling the erectile response by degrading the second messenger product of the erection mediatory nitric oxide (NO) signaling pathway, 3', 5'-cyclic guanosine monophosphate. Accordingly, PDE5 has been targeted for sexual medicine purposes, and orally administered PDE5 inhibitors such as sildenafil, tadalafil, and vardenafil comprise a foremost intervention for erectile dysfunction (ED). New investigation of PDE5 regulation in the penis has suggested alternative roles for the enzyme and new therapeutic opportunities involving its molecular interactions. In particular, PDE5 function is altered under derangements of androgen deficiency, decreased NO bioactivity, and oxidative stress-associated inflammatory changes, thus contributing to an assortment of erectile disorders including hypogonadism-associated ED, recurrent ischemic priapism, penile vasculopathy, and penile fibrosis. This review provides a critical examination of the multifaceted role of the PDE5 regulatory system in the penis and its relevance for applying existing and emerging therapeutic strategies for erectile disorders.