Modulation of the TRPV4 ion channel as a therapeutic target for disease.
File(s)
Author(s)
Grace, MS
Bonvini, SJ
Belvisi, MG
McIntyre, P
Type
Journal Article
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.
Date Issued
2017-02-12
Date Acceptance
2017-02-01
Citation
Pharmacology and Therapeutics, 2017, 177, pp.9-22
ISSN
0163-7258
Publisher
Elsevier
Start Page
9
End Page
22
Journal / Book Title
Pharmacology and Therapeutics
Volume
177
Copyright Statement
© 2017 Elsevier Inc. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/28202366
PII: S0163-7258(17)30033-5
Subjects
Gastrointestinal disease
Inflammation
Oedema
Pain
Respiratory disease
TRPV4
Vascular tone
Publication Status
Published
Coverage Spatial
England