Center for Translational Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Jane and Leonard Korman Respiratory Institute, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Handb Exp Pharmacol. 2022;275:203-227. doi: 10.1007/164_2021_436.
G protein-coupled receptors (GPCRs) play a central role in regulating the functions of a diverse range of cell types in the airway. Taste 2 receptor (T2R) family of GPCRs is responsible for the transduction of bitter taste; however, recent studies have demonstrated that different subtypes of T2Rs and key components of T2R signaling are expressed in several extra-oral tissues including airways with many physiological roles. In the lung, expression of T2Rs has been confirmed in multiple airway cell types including airway smooth muscle (ASM) cells, various epithelial cell subtypes, and on both resident and migratory immune cells. Most importantly, activation of T2Rs with a variety of putative agonists elicits unique signaling in ASM and specialized airway epithelial cells resulting in the inhibition of ASM contraction and proliferation, promotion of ciliary motility, and innate immune response in chemosensory airway epithelial cells. Here we discuss the expression of T2Rs and the mechanistic basis of their function in the structural cells of the airways with some useful insights on immune cells in the context of allergic asthma and other upper airway inflammatory disorders. Emphasis on T2R biology and pharmacology in airway cells has an ulterior goal of exploiting T2Rs for therapeutic benefit in obstructive airway diseases.
G 蛋白偶联受体（GPCRs）在调节气道中多种细胞类型的功能方面发挥着核心作用。味觉 2 受体（T2R）家族 GPCR 负责传递苦味；然而，最近的研究表明，不同亚型的 T2R 和 T2R 信号的关键组成部分在包括气道在内的几种口腔外组织中表达，这些组织具有许多生理作用。在肺部，T2R 在多种气道细胞类型中表达，包括气道平滑肌（ASM）细胞、各种上皮细胞亚型，以及常驻和迁移免疫细胞上。最重要的是，用各种假定的激动剂激活 T2R 会在 ASM 和特化的气道上皮细胞中引发独特的信号转导，从而抑制 ASM 收缩和增殖，促进纤毛运动，并在化学感觉气道上皮细胞中引发先天免疫反应。在这里，我们讨论了 T2R 的表达及其在气道结构细胞中的功能的机制基础，并结合变应性哮喘和其他上呼吸道炎症性疾病中的免疫细胞，提供了一些有用的见解。强调气道细胞中的 T2R 生物学和药理学，其最终目的是利用 T2R 来治疗阻塞性气道疾病。
