cGMP：独特的第二信使分子——cGMP 研究和开发的最新进展,Naunyn-Schmiedeberg s Archives of Pharmacology

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cGMP：独特的第二信使分子——cGMP 研究和开发的最新进展
Naunyn-Schmiedeberg s Archives of Pharmacology Pub Date : 2019-12-18 , DOI: 10.1007/s00210-019-01779-z
Andreas Friebe ₁ , Peter Sandner ₂ , Achim Schmidtko ₃

Affiliation

摘要环磷酸鸟苷 (cGMP) 是在不同细胞类型和组织中形成的独特第二信使分子。cGMP 靶向多种下游效应分子，因此引发多种细胞效应。它的产生是通过刺激可溶性鸟苷酸环化酶 (sGC) 或颗粒性鸟苷酸环化酶 (pGC) 来触发的；两种酶以不同的亚型存在。cGMP 诱导的作用由内源性受体配体（例如一氧化氮 (NO) 和利尿钠肽 (NP)）调节。根据sGC和pGC的分布以及配体的形成，该通路不仅调节心血管系统，还调节肾、肺、肝和脑功能；此外，cGMP途径参与纤维化、炎症或神经变性的发病机制，也可能在疟疾等传染病中发挥作用。此外，正在开发新的药理学方法，以 sGC 和 pGC 依赖性途径为目标，用于治疗各种疾病。因此，从 cGMP 生成的分子基础、鸟苷酸环化酶和 cGMP 下游靶标的结构和功能开始，从头开始了解这一途径至关重要；研究工作还集中于随后的信号级联、它们潜在的串扰，以及 cGMP 调节的转化和最终的临床影响。本综述试图总结 2019 年在美因茨举行的“第九届 cGMP 发生器、效应器和治疗影响国际 cGMP 会议”的贡献。所提供的数据也将根据最近的里程碑式发现和该领域正在进行的活动进行讨论和扩展临床前和临床cGMP研究。

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cGMP: a unique 2nd messenger molecule – recent developments in cGMP research and development

AbstractCyclic guanosine monophosphate (cGMP) is a unique second messenger molecule formed in different cell types and tissues. cGMP targets a variety of downstream effector molecules and, thus, elicits a very broad variety of cellular effects. Its production is triggered by stimulation of either soluble guanylyl cyclase (sGC) or particulate guanylyl cyclase (pGC); both enzymes exist in different isoforms. cGMP-induced effects are regulated by endogenous receptor ligands such as nitric oxide (NO) and natriuretic peptides (NPs). Depending on the distribution of sGC and pGC and the formation of ligands, this pathway regulates not only the cardiovascular system but also the kidney, lung, liver, and brain function; in addition, the cGMP pathway is involved in the pathogenesis of fibrosis, inflammation, or neurodegeneration and may also play a role in infectious diseases such as malaria. Moreover, new pharmacological approaches are being developed which target sGC- and pGC-dependent pathways for the treatment of various diseases. Therefore, it is of key interest to understand this pathway from scratch, beginning with the molecular basis of cGMP generation, the structure and function of both guanylyl cyclases and cGMP downstream targets; research efforts also focus on the subsequent signaling cascades, their potential crosstalk, and also the translational and, ultimately, the clinical implications of cGMP modulation. This review tries to summarize the contributions to the “9th International cGMP Conference on cGMP Generators, Effectors and Therapeutic Implications” held in Mainz in 2019. Presented data will be discussed and extended also in light of recent landmark findings and ongoing activities in the field of preclinical and clinical cGMP research.

更新日期：2019-12-18

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