Penn Raymond B
Department of Internal Medicine, Wake Forest University Health Sciences Center, Winston-Salem, NC 27157, USA.
Naunyn Schmiedebergs Arch Pharmacol. 2008 Aug;378(2):149-69. doi: 10.1007/s00210-008-0263-1. Epub 2008 Feb 16.
G protein-coupled receptors (GPCRs) regulate numerous airway cell functions, and signaling events transduced by GPCRs are important in both asthma pathogenesis and therapy. Indeed, most asthma therapies target GPCRs either directly or indirectly. Within recent years, our understating of how GPCRs signal and are regulated has changed significantly as new concepts have emerged and traditional ideas have evolved. In this review, we discuss current concepts regarding constitutive GPCR activity and receptor agonism, functional selectivity, compartmentalized signaling, and GPCR desensitization. We further discuss the relevance of these ideas to asthma and asthma therapy, while emphasizing their potential application to the GPCR signaling in airway smooth muscle that regulates airway patency and thus disease severity.
G蛋白偶联受体（GPCRs）调节多种气道细胞功能，GPCRs转导的信号事件在哮喘发病机制和治疗中均很重要。事实上，大多数哮喘治疗方法直接或间接靶向GPCRs。近年来，随着新概念的出现和传统观念的演变，我们对GPCRs如何发出信号以及如何被调节的理解发生了显著变化。在本综述中，我们讨论了关于组成型GPCR活性和受体激动作用、功能选择性、区室化信号传导以及GPCR脱敏的当前概念。我们进一步讨论了这些概念与哮喘和哮喘治疗的相关性，同时强调它们在调节气道通畅性从而影响疾病严重程度的气道平滑肌GPCR信号传导中的潜在应用。
