Wright Peter T, Schobesberger Sophie, Gorelik Julia
Functional Microscopy, Myocardial Function, National Heart and Lung Institute, Imperial College London , Du Cane Road, London, UK.
Front Pharmacol. 2015 Jul 17;6:148. doi: 10.3389/fphar.2015.00148. eCollection 2015.
Signal transduction via G-protein coupled receptors (GPCRs) relies upon the production of cAMP and other signaling cascades. A given receptor and agonist pair, produce multiple effects upon cellular physiology which can be opposite in different cell types. The production of variable cellular effects via the signaling of the same GPCR in different cell types is a result of signal organization in space and time (compartmentation). This organization is usually based upon the physical and chemical properties of the membranes in which the GPCRs reside and the repertoire of downstream effectors and co-factors that are available at that location. In this review we explore mechanisms of GPCR signal compartmentation and broadly review the state-of-the-art methodologies which can be utilized to study them. We provide a clear rationale for a "localized" approach to the study of the pharmacology and physiology of GPCRs and particularly the secondary messenger cAMP.
通过G蛋白偶联受体（GPCRs）进行的信号转导依赖于cAMP和其他信号级联反应的产生。特定的受体和激动剂对会对细胞生理学产生多种影响，而这些影响在不同细胞类型中可能是相反的。在不同细胞类型中，通过同一GPCR的信号传导产生可变的细胞效应是信号在空间和时间上组织（区室化）的结果。这种组织通常基于GPCRs所在膜的物理和化学性质，以及该位置可用的下游效应器和辅助因子的组成。在本综述中，我们探讨了GPCR信号区室化的机制，并广泛回顾了可用于研究这些机制的最新方法。我们为研究GPCRs药理学和生理学，特别是第二信使cAMP提供了一种“局部化”方法的明确理论依据。
