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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Preliminary X-Ray Crystallographic Studies of a Lys49-Phospholipase A2 Homologue from Bothrops pirajai Venom Complexed with p-Bromophenacyl Bromide and α-Tocopherol Inhibitors
Protein & Peptide Letters Monoclonal Antibodies as Cancer Therapeutics
Recent Patents on Biotechnology Mitochondrial Dysfunction and Antioxidant Therapy in Sepsis
Infectious Disorders - Drug Targets Natriuretic Peptide Guided Heart Failure Management
Current Clinical Pharmacology Physiological Effect and Therapeutic Application of Alpha Lipoic Acid
Current Medicinal Chemistry Reducing the Risk of Major Elective Non-cardiac Surgery: Is there a Role for Levosimendan in the Preoperative Optimization of Cardiac Function?
Current Drug Targets Comparison of the Mean Minimum Dose of Bolus Oxytocin for Proper Uterine Contraction during Cesarean Section
Current Clinical Pharmacology PPARγ in Angiogenesis and Vascular Development
Current Angiogenesis (Discontinued) Acute Antithrombotic Treatment of Ischemic Stroke
Current Vascular Pharmacology The Possible Adverse Effects of Intramuscular Botulinum Toxin Injections and their Management
Current Drug Safety The Opioid Receptor Independent Actions of Kappa Receptor Agonists in the Cardiovascular System
Current Pharmaceutical Design Moving Troponin Testing into the 21st Century: Will Greater Sensitivity Be Met with Greater Sensibility?
Cardiovascular & Hematological Disorders-Drug Targets The Pharmacological Effects of Novokinin; a Designed Peptide Agonist of the Angiotensin AT<sab>2</sab> Receptor
Current Pharmaceutical Design Emerging Antimicrobial Applications of Nitric Oxide (NO) and NO-Releasing Materials
Anti-Infective Agents in Medicinal Chemistry Small Molecules in Treatment of Sepsis
Current Drug Targets Joshanda: A Traditional Herbal Approach for Treatment of Respiratory Catarrh
Current Respiratory Medicine Reviews Therapeutic Medical Hypothermia-A Multispecialty Approach
Recent Patents on Cardiovascular Drug Discovery Emerging Role of Cetuximab in the Treatment of Colorectal Cancer
Recent Patents on Anti-Cancer Drug Discovery Beyond the "Lock and Key" Paradigm: Targeting Lipid Rafts to Induce the Selective Apoptosis of Cancer Cells
Current Medicinal Chemistry An Overview of Non-Neural Sources of Calcitonin Gene-Related Peptide
Current Medicinal Chemistry