Targeting TRP channels in airway disorders.
Targeting TRP channels in airway disorders.
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针对气道疾病中的 TRP 通道。
DOI：
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发表时间：
2013
影响因子：
3.4
通讯作者：
J. M. Verkuyl
中科院分区：
文献类型：
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作者：
K. Abbott;C. Poll;J. M. Verkuyl
人们正在积极寻求新的有效治疗药物，以治疗广泛的呼吸系统疾病，这些疾病对全世界数亿人的死亡率、发病率和生活质量产生重大影响。这些疾病包括哮喘、过敏性鼻炎、慢性阻塞性肺病、咳嗽、特发性肺纤维化、肺动脉高压、囊性纤维化和急性肺损伤。TRP通道广泛分布于整个呼吸道，在感知和随后响应各种刺激（如温度、渗透压和氧化应激）方面发挥重要的生理作用。然而，在呼吸系统疾病的情况下，TRP通道功能可能发生改变，例如：在氧化应激、炎症、缺氧和机械应力的情况下。此外，有证据表明，TRP通道的表达/活性可以在疾病环境中受到影响。因此，包括呼吸系统疾病在内的一系列疾病正在研究TRP通道功能的调节剂。几篇优秀的综述文章详细讨论了特定TRP通道的调节可能对特定呼吸系统疾病有益的证据。在本文中，我们回顾了TRP通道功能的调节可能影响呼吸系统疾病的共同和重叠特征的证据，例如支气管收缩、气道高反应性、咳嗽、气道炎症、粘液分泌过多、加重、肺损伤、缺氧和气道重塑。本文还讨论了TRP通道调节剂的治疗潜力，这些药物在临床中的地位以及在这一快速发展的领域所面临的挑战。
Novel effective therapeutic agents are actively sought for the treatment of a broad spectrum of respiratory diseases which collectively significantly impact on mortality, morbidity and quality of life of hundreds of millions of people world-wide. These include asthma, allergic rhinitis, chronic obstructive pulmonary disease, cough, idiopathic pulmonary fibrosis, pulmonary arterial hypertension, cystic fibrosis and acute lung injury. TRP channels are broadly distributed throughout the respiratory tract and play an important physiological role in sensing and subsequently responding to a wide variety of stimuli, for example temperature, osmolarity and oxidant stress. In the context of respiratory disease however TRP channel function may be altered, eg: under conditions of oxidative stress, inflammation, hypoxia and mechanical stress. In addition there is evidence that the expression/activity of TRP channels can be affected in the disease setting. Modulators of TRP channel function are therefore under investigation for a range of diseases including disorders of the respiratory system. Several excellent review articles have discussed in detail evidence that modulation of specific TRP channels may be of benefit in specific respiratory diseases. In this article we have taken the approach of reviewing evidence that modulation of TRP channel function may be able to affect common and over-lapping characteristic features of respiratory diseases, for example bronchoconstriction, airways hyper-responsiveness, cough, airways inflammation, mucus hyper-secretion, exacerbations, lung injury, hypoxia and airways re-modelling. The therapeutic potential of TRP channel modulators, the status of these agents in the clinic along with the challenges posed in this rapidly advancing field are also discussed in this review.