Abstract
TRPV4 belongs to the TRPV subfamily of Transient Receptor Potential (TRP) ion channels. This year marks the 10 year anniversary of the discovery of this polymodal ion channel which is activated by a variety of stimuli including warm temperatures, hypotonicity and endogenous lipids. Coupled with a widespread tissue distribution, this activation profile has resulted in a large number of disparate physiological functions for TRPV4. These range from temperature monitoring in skin keratinocytes to osmolarity sensing in kidneys, sheer stress detection in blood vessels and osteoclast differentiation control in bone. As knowledge of its physiological roles has expanded, interest in targeting TRPV4 modulation for therapeutic purposes has arisen and is now focused on several areas. First, as with related TRP channels TRPV1, TRPV3, TRPM8 and TRPA1, TRPV4 antagonism is being considered for inflammatory and neuropathic pain treatment. Recent work conducted using KO mice and agonists 4αPDD and GSK1016790A suggests bladder dysfunctions may also be targeted. Additionally, ventilator-induced lung injury has emerged as another potential indication for TRPV4 antagonists. Herein we review the known small molecule modulators of TRPV4 and relate progress made in identifying potent, selective and bioavailable agonists and antagonists to interrogate this ion channel in vivo.
Keywords: 4αPDD, activator, blocker, GSK1016790A, inhibitor, phorbol ester, RN-1747, RN-1734, ruthenium red, TRPV4, polymodal ion channel, temperature monitoring in skin, keratinocytes, osmolarity sensing in kidneys, sheer stress detection in blood vessels
Current Topics in Medicinal Chemistry
Title: TRPV4 Agonists and Antagonists
Volume: 11 Issue: 17
Author(s): Fabien Vincent and Matthew A.J. Duncton
Affiliation:
Keywords: 4αPDD, activator, blocker, GSK1016790A, inhibitor, phorbol ester, RN-1747, RN-1734, ruthenium red, TRPV4, polymodal ion channel, temperature monitoring in skin, keratinocytes, osmolarity sensing in kidneys, sheer stress detection in blood vessels
Abstract: TRPV4 belongs to the TRPV subfamily of Transient Receptor Potential (TRP) ion channels. This year marks the 10 year anniversary of the discovery of this polymodal ion channel which is activated by a variety of stimuli including warm temperatures, hypotonicity and endogenous lipids. Coupled with a widespread tissue distribution, this activation profile has resulted in a large number of disparate physiological functions for TRPV4. These range from temperature monitoring in skin keratinocytes to osmolarity sensing in kidneys, sheer stress detection in blood vessels and osteoclast differentiation control in bone. As knowledge of its physiological roles has expanded, interest in targeting TRPV4 modulation for therapeutic purposes has arisen and is now focused on several areas. First, as with related TRP channels TRPV1, TRPV3, TRPM8 and TRPA1, TRPV4 antagonism is being considered for inflammatory and neuropathic pain treatment. Recent work conducted using KO mice and agonists 4αPDD and GSK1016790A suggests bladder dysfunctions may also be targeted. Additionally, ventilator-induced lung injury has emerged as another potential indication for TRPV4 antagonists. Herein we review the known small molecule modulators of TRPV4 and relate progress made in identifying potent, selective and bioavailable agonists and antagonists to interrogate this ion channel in vivo.
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Cite this article as:
Vincent Fabien and A.J. Duncton Matthew, TRPV4 Agonists and Antagonists, Current Topics in Medicinal Chemistry 2011; 11 (17) . https://dx.doi.org/10.2174/156802611796904861
DOI https://dx.doi.org/10.2174/156802611796904861 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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