Autonomic Neuroscience Centre, University College Medical School, Royal Free Campus, London, UK.
Pharmacol Rev. 2012 Oct;64(4):834-68. doi: 10.1124/pr.111.005389. Epub 2012 Aug 10.
Evidence for a significant role and impact of purinergic signaling in normal and diseased airways is now beyond dispute. The present review intends to provide the current state of knowledge of the involvement of purinergic pathways in the upper and lower airways and lungs, thereby differentiating the involvement of different tissues, such as the epithelial lining, immune cells, airway smooth muscle, vasculature, peripheral and central innervation, and neuroendocrine system. In addition to the vast number of well illustrated functions for purinergic signaling in the healthy respiratory tract, increasing data pointing to enhanced levels of ATP and/or adenosine in airway secretions of patients with airway damage and respiratory diseases corroborates the emerging view that purines act as clinically important mediators resulting in either proinflammatory or protective responses. Purinergic signaling has been implicated in lung injury and in the pathogenesis of a wide range of respiratory disorders and diseases, including asthma, chronic obstructive pulmonary disease, inflammation, cystic fibrosis, lung cancer, and pulmonary hypertension. These ostensibly enigmatic actions are based on widely different mechanisms, which are influenced by the cellular microenvironment, but especially the subtypes of purine receptors involved and the activity of distinct members of the ectonucleotidase family, the latter being potential protein targets for therapeutic implementation.
嘌呤能信号在正常和患病气道中的重要作用和影响的证据现在已经毋庸置疑。本综述旨在提供嘌呤能途径在上呼吸道和下呼吸道及肺部的参与的最新知识，从而区分不同组织的参与，如上皮衬里、免疫细胞、气道平滑肌、血管、周围和中枢神经支配以及神经内分泌系统。除了嘌呤能信号在健康呼吸道中具有大量功能的大量说明外，越来越多的证据表明，气道损伤和呼吸系统疾病患者的气道分泌物中 ATP 和/或腺苷水平升高，这证实了嘌呤作为具有临床重要意义的介质的观点，导致促炎或保护反应。嘌呤能信号参与肺损伤和多种呼吸系统疾病和病症的发病机制，包括哮喘、慢性阻塞性肺疾病、炎症、囊性纤维化、肺癌和肺动脉高压。这些看似神秘的作用基于广泛不同的机制，这些机制受细胞微环境的影响，但特别是涉及的嘌呤受体亚型和核苷酸酶家族的不同成员的活性，后者是治疗实施的潜在蛋白质靶标。
