Feil Robert, Lehners Moritz, Stehle Daniel, Feil Susanne
Interfakultäres Institut für Biochemie, University of Tübingen, Tübingen, Germany.
Br J Pharmacol. 2022 Jun;179(11):2394-2412. doi: 10.1111/bph.15500. Epub 2021 May 22.
cGMP is an important signalling molecule in humans. Fluorescent cGMP biosensors have emerged as powerful tools for the sensitive analysis of cGMP pathways at the single-cell level. Here, we briefly outline cGMP's multifaceted role in (patho)physiology and pharmacotherapy. Then we summarise what new insights cGMP imaging has provided into endogenous cGMP signalling and drug action, with a focus on the cardiovascular system. Indeed, the use of cGMP biosensors has led to several conceptual advances, such as the discovery of local, intercellular and mechanosensitive cGMP signals. Importantly, single-cell imaging can provide valuable information about the heterogeneity of cGMP signals within and between individual cells of an isolated cell population or tissue. We also discuss current challenges and future directions of cGMP imaging, such as the direct visualisation of cGMP microdomains, simultaneous monitoring of cGMP and other signalling molecules and, ultimately, cGMP imaging in tissues and animals under close-to-native conditions. 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.
环磷酸鸟苷（cGMP）是人体内一种重要的信号分子。荧光cGMP生物传感器已成为在单细胞水平上对cGMP信号通路进行灵敏分析的强大工具。在此，我们简要概述cGMP在（病理）生理学和药物治疗中的多方面作用。然后我们总结cGMP成像在内源性cGMP信号传导和药物作用方面提供的新见解，重点关注心血管系统。事实上，cGMP生物传感器的使用带来了一些概念上的进展，例如发现了局部、细胞间和机械敏感的cGMP信号。重要的是，单细胞成像可以提供有关分离的细胞群体或组织中单个细胞内部和之间cGMP信号异质性的有价值信息。我们还讨论了cGMP成像当前面临的挑战和未来方向，例如cGMP微区的直接可视化、cGMP与其他信号分子的同时监测，以及最终在接近自然条件下对组织和动物进行cGMP成像。相关文章：本文是关于细胞生长和存活中cGMP信号传导的主题特刊的一部分。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。
