Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University Health Sciences Center, Mercer University, Atlanta, GA 30341, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University Health Sciences Center, Mercer University, Atlanta, GA 30341, USA.
Biochem Pharmacol. 2020 Jan;171:113690. doi: 10.1016/j.bcp.2019.113690. Epub 2019 Nov 5.
β2-Adrenergic receptor (β2AR) agonists are clinically used to elicit rapid bronchodilation for the treatment of bronchospasms in pulmonary diseases such as asthma and COPD, both of which exhibit characteristically high levels of reactive oxygen species (ROS); likely secondary to over-expression of ROS generating enzymes and chronically heightened inflammation. Interestingly, β2AR has long-been linked to ROS, yet the involvement of ROS in β2AR function has not been as vigorously studied as other aspects of β2AR signaling. Herein, we discuss the existing body of evidence linking β2AR activation to intracellular ROS generation and importantly, the role of ROS in regulating β2AR function. The reciprocal interplay of the β2AR and ROS appear to endow this receptor with the ability to self-regulate signaling efficacy and ligand binding, hereby unveiling a redox-axis that may be unfavorably altered in pathological states contributing to both disease progression and therapeutic drug responses.
β2-肾上腺素能受体 (β2AR) 激动剂临床上用于诱发支气管扩张以治疗哮喘和 COPD 等肺部疾病中的支气管痉挛，这些疾病都表现出高水平的活性氧物种 (ROS)；可能是由于 ROS 生成酶的过度表达和慢性炎症升高所致。有趣的是，β2AR 长期以来一直与 ROS 有关，但 ROS 在 β2AR 功能中的作用并没有像其他方面的 β2AR 信号那样得到广泛研究。在此，我们讨论将β2AR 激活与细胞内 ROS 生成联系起来的现有证据，以及 ROS 在调节 β2AR 功能中的作用。β2AR 和 ROS 的相互作用似乎赋予了该受体自我调节信号效率和配体结合的能力，从而揭示了一种氧化还原轴，在导致疾病进展和治疗药物反应的病理状态下，这种氧化还原轴可能会发生不利改变。
