title: Modulation of the TRPV4 ion channel as a therapeutic target for disease.
abstract: Transient Receptor Potential Vanilloid 4 (TRPV4) is a broadly expressed, polymodally gated ion channel that plays an important role in many physiological and pathophysiological processes. TRPV4 knockout mice and several synthetic pharmacological compounds that selectively target TRPV4 are now available, which has allowed detailed investigation in to the therapeutic potential of this ion channel. Results from animal studies suggest that TRPV4 antagonism has therapeutic potential in oedema, pain, gastrointestinal disorders, and lung diseases such as cough, bronchoconstriction, pulmonary hypertension, and acute lung injury. A lack of observed side-effects in vivo has prompted a first-in-human trial for a TRPV4 antagonist in healthy participants and stable heart failure patients. If successful, this would open up an exciting new area of research for a multitude of TRPV4-related pathologies. This review will discuss the known roles of TRPV4 in disease, and highlight the possible implications of targeting this important cation channel for therapy.
authors.affiliation: Baker Heart and Diabetes Institute, Melbourne, Australia; School of Health and Biomedical Sciences, RMIT University, Bundoora, Melbourne, Australia; Department of Physiology, School of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia. Electronic address: megan.grace@baker.edu.au.
authors.forename: Megan S
authors.initials: MS
authors.lastname: Grace
authors.affiliation: Respiratory Pharmacology, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Bonvini
authors.affiliation: Respiratory Pharmacology, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Belvisi
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Bundoora, Melbourne, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: McIntyre
mesh_terms: D000818:Animals; D004487:Edema / Q000188:drug therapy / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy / Q000378:metabolism; D010146:Pain / Q000188:drug therapy / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D050916:TRPV Cation Channels; C416986:TRPV4 protein, human
keywords: Gastrointestinal disease; Inflammation; Oedema; Pain; Respiratory disease; TRPV4; Vascular tone