Liggett Stephen B
Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
J Allergy Clin Immunol. 2002 Dec;110(6 Suppl):S223-7. doi: 10.1067/mai.2002.129945.
The proposed manner by which beta(2)-adrenergic receptors signal has dramatically changed from earlier concepts that centered on a lock-and-key mechanism in which the receptor acts as a simple switch. We now know that beta(2)-adrenergic receptors spontaneously toggle to an activated state (R*) and that the equilibrium between R (the inactive state) and R* can be altered by ligands. In addition, the R* conformation is likely to consist of multiple subspecies that may favor certain signaling pathways or regulatory events. Changes in agonist structure alter the abundance of certain subspecies of R*. Indeed, multifunctional coupling is common with many G-protein-coupled receptors and can be modulated pharmacologically to attain specific outcomes. In addition to providing the basis for development of new beta-agonists for unique signaling, these properties can be extended such that beta(2)-adrenergic receptors, or highly modified "designer" receptors, can be used for gene therapy with highly specific effects.
β₂ - 肾上腺素能受体的信号传导方式与早期以锁钥机制为核心的概念相比发生了巨大变化，早期概念认为受体就像一个简单的开关。我们现在知道，β₂ - 肾上腺素能受体可自发切换到激活状态（R*），并且R（非激活状态）与R之间的平衡可被配体改变。此外，R构象可能由多个亚类组成，这些亚类可能有利于某些信号通路或调节事件。激动剂结构的变化会改变某些R*亚类的丰度。事实上，多功能偶联在许多G蛋白偶联受体中很常见，并且可以通过药理学方法进行调节以获得特定结果。除了为开发具有独特信号传导的新型β激动剂提供基础外，这些特性还可以扩展，使得β₂ - 肾上腺素能受体或经过高度修饰的“设计”受体可用于具有高度特异性作用的基因治疗。
