Friebe Andreas, Englert Nils
Physiological Institute, Julius Maximilian University of Würzburg, Würzburg, Germany.
Br J Pharmacol. 2022 Jun;179(11):2328-2343. doi: 10.1111/bph.15345. Epub 2021 Jan 15.
In the late 1960s, several labatories identified guanylyl cyclase (GC) as the cGMP-producing enzyme. Subsequently, two different types of GC were described that differed in their cellular localization. Primarily found in the cytosol, nitric oxide (NO)-sensitive guanylyl cyclase (NO-GC) acts as receptor for the signalling molecule NO, in contrast the membrane-bound isoenzyme is activated by natriuretic peptides. The lung compared with other tissues exhibits the highest expression of NO-GC. The enzyme has been purified from lung for biochemical analysis. Although expressed in smooth muscle cells (SMCs) and in pericytes, the function of NO-GC in lung, especially in pericytes, is still not fully elucidated. However, pharmacological compounds that target NO-GC are available and have been implemented for the therapy of pulmonary arterial hypertension. In addition, NO-GC has been suggested as drug target for the therapy of asthma, acute respiratory distress syndrome and pulmonary fibrosis. LINKED ARTICLES: This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc.
20世纪60年代末，几家实验室鉴定出鸟苷酸环化酶（GC）是产生环磷酸鸟苷（cGMP）的酶。随后，人们描述了两种不同类型的GC，它们在细胞定位上有所不同。主要存在于胞质溶胶中的一氧化氮（NO）敏感型鸟苷酸环化酶（NO-GC）作为信号分子NO的受体，相比之下，膜结合同工酶则由利钠肽激活。与其他组织相比，肺中NO-GC的表达最高。该酶已从肺中纯化出来用于生化分析。尽管在平滑肌细胞（SMC）和周细胞中表达，但NO-GC在肺中的功能，尤其是在周细胞中的功能仍未完全阐明。然而，针对NO-GC的药理化合物已经存在，并已用于治疗肺动脉高压。此外，NO-GC已被建议作为治疗哮喘、急性呼吸窘迫综合征和肺纤维化的药物靶点。相关文章：本文是关于细胞生长和存活中cGMP信号传导的主题问题的一部分。要查看本节中的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc。
