BETA ADRENERGIC RECEPTOR REGULATION IN HUMAN AIRWAY MUSC

描述（根据申请人的摘要和具体目标改编）： 气道平滑肌上的β-肾上腺素能受体（b2 ARs）在调节气道平滑肌的功能中起重要作用。 调节气道平滑肌张力和气道通畅性的作用， β-拟交感神经药物是哮喘治疗中最广泛使用的药物 并被公认为急性哮喘的首选治疗方法 攻击 尽管β-受体激动剂的临床重要性和良好的 了解b2 AR激活如何促进气道平滑肌 放松，令人惊讶的是，很少有人知道的方式， b2 AR信号通路在气道平滑肌中受到调节。 长期 该项目的目的是描述分子和细胞 相关的生理因子，如炎症因子， 介质、糖皮质激素和β受体激动剂本身会改变b2 AR 人气道平滑肌（HASM）的反应性。 具体目标是： 1)减敏和从减敏中恢复的表征 HASM细胞中b2 AR功能的研究; 2）主要的 脱敏过程中b2 AR信号调节的机制 和再敏化过程;和3）鉴定蛋白质的作用 在这些过程中。

DESCRIPTION (Adapted from applicant's abstract and specific aims): Beta-adrenergic receptors (b2ARs) on airway smooth muscle play an important role in regulating airway smooth muscle tone and airway patency, while beta-sympathomimetic drugs are the most widely used agents in asthma therapy and are universally recognized as the treatment of choice for acute asthma attacks. Despite the clinical importance of beta-agonists and a good understanding of how b2AR activation promotes airway smooth muscle relaxation, surprisingly little is known regarding the manner in which the b2AR signaling pathway is regulated in airway smooth muscle. The long-term objective of this project is to delineate the molecular and cellular mechanisms by which relevant physiological agents, such as inflammatory mediators, glucocorticoids, and beta-agonists themselves, alter b2AR responsiveness in human airway smooth muscle (HASM). The specific aims are: 1) characterization of the desensitization and recovery from desensitization of b2AR function in HASM cells; 2) characterization of the principal mechanisms by which b2AR signaling is regulated during the desensitization and resensitization processes; and 3) identification of the role of protein kinases in these processes.