TRPV4: physiological role and therapeutic potential in respiratory diseases

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• 作者：Neil M. Goldenberg (1) (2)
  Krishnan Ravindran (2)
  Wolfgang M. Kuebler (2) (3) (4) (5)
  
  1. Department of Anesthesia ; University of Toronto ; Toronto ; ON ; Canada
  2. The Keenan Research Centre at the Li Ka Shing Knowledge Institute of St. Michael鈥檚 Hospital ; 30 Bond Street ; Bond Wing 2-021 ; Toronto ; ON ; M5B 1W8 ; Canada
  3. German Heart Institute ; Berlin ; Germany
  4. Institute of Physiology ; Charit茅-Universit盲tsmedizin Berlin ; Berlin ; Germany
  5. Departments of Surgery and Physiology ; University of Toronto ; Toronto ; ON ; Canada
  
• 关键词：TRPV4 structure ; Transient receptor potential ; Acute lung injury
• 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：388
• 期：4
• 页码：421-436
• 全文大小：1,142 KB
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  Neurosciences
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1912

文摘

Members of the family of transient receptor potential (TRP) channels have been implicated in the pathophysiology of a host of lung diseases. The role of these multimodal cation channels in lung homeostasis is thought to stem from their ability to respond to changes in mechanical stimuli (i.e., shear and stretch), as well as to various protein and lipid mediators. The vanilloid subfamily member, TRPV4, which is highly expressed in the majority of lung cell types, is well positioned for critical involvement in several pulmonary conditions, including edema formation, control of pulmonary vascular tone, and the lung response to local or systemic inflammatory insults. In recent years, several pharmacological inhibitors of TRPV4 have been developed, and the current generation of compounds possess high affinity and specificity for TRPV4. As such, we have now entered a time where the therapeutic potential of TRPV4 inhibitors can be systematically examined in a variety of lung diseases. Due to this fact, this review seeks to describe the current state of the art with respect to the role of TRPV4 in pulmonary homeostasis and disease, and to highlight the current and future roles of TRPV4 inhibitors in disease treatment. We will first focus on genera aspects of TRPV4 structure and function, and then will discuss known roles for TRPV4 in pulmonary diseases, including pulmonary edema formation, pulmonary hypertension, and acute lung injury. Finally, both promising aspects and potential pitfalls of the clinical use of TRPV4 inhibitors will be examined.