Department of Pulmonary Medicine, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Curr Opin Pharmacol. 2010 Jun;10(3):254-9. doi: 10.1016/j.coph.2010.03.002.
Beta(2)-adrenoceptor (beta(2)-AR) agonists are very effective bronchodilators and play a major role in every stage of asthma management. However, their chronic, regular use is associated with detrimental effects including an increase in asthma-related deaths. Conversely, recent data suggest that certain beta-blockers, specifically beta-adrenoceptor (beta-AR) inverse agonists, may be useful in the chronic treatment of asthma. Here we review the data for this observation and the signaling pathways that may be involved. The data suggest that beta(2)-AR signaling is required to produce maximal airway inflammation and hyperresponsiveness, and the signaling pathway responsible for these effects is likely the non-canonical beta-arrestin-2 pathway. Therefore, beta-AR inverse agonists may produce their beneficial chronic effects by inhibiting constitutive or ligand-induced activation of this pathway. Both lung parenchymal and hematopoietic cells appear to be involved in mediating the beneficial effects of beta-AR inverse agonists.
β2-肾上腺素受体（β2-AR）激动剂是非常有效的支气管扩张剂，在哮喘管理的各个阶段都发挥着重要作用。然而，它们的慢性、常规使用与有害影响有关，包括哮喘相关死亡的增加。相反，最近的数据表明，某些β-受体阻滞剂，特别是β-肾上腺素受体（β-AR）反向激动剂，可能对哮喘的慢性治疗有用。在这里，我们回顾了这一观察结果的数据以及可能涉及的信号通路。这些数据表明，β2-AR 信号对于产生最大的气道炎症和高反应性是必需的，而负责这些效应的信号通路可能是非经典的β-arrestin-2 通路。因此，β-AR 反向激动剂可能通过抑制该途径的组成型或配体诱导激活来产生其有益的慢性作用。肺实质细胞和造血细胞似乎都参与了介导β-AR 反向激动剂的有益作用。
