Department of Molecular Pharmacology, University of Groningen, the Netherlands; Institute of Experimental Cardiovascular Research, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany.
Department of Molecular Pharmacology, University of Groningen, the Netherlands; Groningen Research Institute for Asthma and COPD, GRIAC, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Pharmacol Ther. 2019 May;197:225-242. doi: 10.1016/j.pharmthera.2019.02.002. Epub 2019 Feb 10.
Chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma, affect millions of people all over the world. Cyclic adenosine monophosphate (cAMP) which is one of the most important second messengers, plays a vital role in relaxing airway smooth muscles and suppressing inflammation. Given its vast role in regulating intracellular responses, cAMP provides an attractive pharmaceutical target in the treatment of chronic respiratory diseases. Phosphodiesterases (PDEs) are enzymes that hydrolyze cyclic nucleotides and help control cyclic nucleotide signals in a compartmentalized manner. Currently, the selective PDE4 inhibitor, roflumilast, is used as an add-on treatment for patients with severe COPD associated with bronchitis and a history of frequent exacerbations. In addition, other novel PDE inhibitors are in different phases of clinical trials. The current review provides an overview of the regulation of various PDEs and the potential application of selective PDE inhibitors in the treatment of COPD and asthma. The possibility to combine various PDE inhibitors as a way to increase their therapeutic effectiveness is also emphasized.
慢性呼吸系统疾病，如慢性阻塞性肺疾病（COPD）和哮喘，影响着全世界数百万人。环磷酸腺苷（cAMP）作为最重要的第二信使之一，在气道平滑肌松弛和抑制炎症方面发挥着至关重要的作用。鉴于其在调节细胞内反应方面的广泛作用，cAMP 为治疗慢性呼吸系统疾病提供了一个有吸引力的药物靶点。磷酸二酯酶（PDEs）是水解环核苷酸的酶，有助于以区室化的方式控制环核苷酸信号。目前，选择性 PDE4 抑制剂罗氟司特被用作伴有支气管炎和频繁恶化史的严重 COPD 患者的附加治疗药物。此外，其他新型 PDE 抑制剂处于不同的临床试验阶段。本综述提供了对各种 PDE 的调节以及选择性 PDE 抑制剂在 COPD 和哮喘治疗中的潜在应用的概述。还强调了将各种 PDE 抑制剂联合使用以提高其治疗效果的可能性。
