BETA ADRENERGIC RECEPTOR REGULATION IN HUMAN AIRWAY MUSC

描述(根据申请者的抽象和具体目标改编)： 气道平滑肌上的β-肾上腺素能受体(B2ARs)起重要作用 在调节气道平滑肌张力和气道通畅性方面的作用，而 β-交感神经药物是哮喘治疗中应用最广泛的药物。 被公认为是治疗急性哮喘的首选药物 袭击。尽管β-激动剂的临床重要性和良好的 B2AR激活如何促进气道平滑肌的研究 放松，令人惊讶的是，人们对这种行为的方式知之甚少 B2AR信号通路在气道平滑肌中有调节作用。长期的 这个项目的目标是描绘出分子和细胞 炎症等相关生理因素的作用机制 介质、糖皮质激素和β-激动剂本身会改变B2AR 人呼吸道平滑肌(HASM)的反应性。具体目标是： 1)脱敏和脱敏恢复的表征 HASM细胞中B2AR功能的研究；2)主要 B2AR信号在脱敏过程中的调控机制 和再敏化过程；以及3)确定蛋白质的作用 这些过程中的蛋白水解酶。

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.