Systemic Activation of the Transient Receptor Potential Vanilloid Subtype 4 Channel Causes Endothelial Failure and Circulatory Collapse: Part 2
Abstract
The transient receptor potential (TRP) vanilloid subtype 4 (V4) is a nonselective cation channel that exhibits polymodal activation and is expressed in the endothelium, where it contributes to intracellular Ca2+ homeostasis and regulation of cell volume. The purpose of the present study was to evaluate the systemic cardiovascular effects of GSK1016790A, a novel TRPV4 activator, and to examine its mechanism of action. In three species (mouse, rat, and dog), the i.v. administration of GSK1016790A induced a dose-dependent reduction in blood pressure, followed by profound circulatory collapse. In contrast, GSK1016790A had no acute cardiovascular effects in the TRPV4-/- null mouse. Hemodynamic analyses in the dog and rat demonstrate a profound reduction in cardiac output. However, GSK1016790A had no effect on rate or contractility in the isolated, buffer-perfused rat heart, and it produced potent endothelial-dependent relaxation of rodent-isolated vascular ring segments that were abolished by nitric-oxide synthase (NOS) inhibition (N-nitro-L-arginine methyl ester; L-NAME), ruthenium red, and endothelial NOS (eNOS) gene deletion. However, the in vivo circulatory collapse was not altered by NOS inhibition (L-NAME) or eNOS gene deletion but was associated with (concentration and time appropriate) profound vascular leakage and tissue hemorrhage in the lung, intestine, and kidney. TRPV4 immunoreactivity was localized in the endothelium and epithelium in the affected organs. GSK1016790A potently induced rapid electrophysiological and morphological changes (retraction/condensation) in cultured endothelial cells. In summary, inappropriate activation of TRPV4 produces acute circulatory collapse associated with endothelial activation/injury and failure of the pulmonary microvascular permeability barrier. It will be important to determine the role of TRPV4 in disorders associated with edema and microvascular congestion.
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HUVECs may not entirely recapitulate all known roles for TRPV4 in tumor vasculature.
“HUVECs may not entirely recapitulate all known roles for TRPV4 in tumor vasculature. 24,28,35,51,53,66”
From Rapid Assessment of Nanoparticle Extravasation in a Microfluidic Tumor Model (2019) · cites this paper as [24]
Cites
Guide for the Care and Use of Laboratory Animals: Eighth Edition
(2011) · doi:10.17226/12910 · Cited by 16,199 · see citing works
Liedtke, W., Choe, Y., Martı́-Renom, M. A., Bell, A. M., Denis, C. S., AndrejŠali, Hudspeth, A. J., Friedman, J. M., & Heller, S. (2000) · Cell · doi:10.1016/s0092-8674(00)00143-4 · Cited by 1,391 · see citing works
Cellular regulation of endothelial nitric oxide synthase
Govers, R., & Rabelink, T. J. (2001) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.2001.280.2.f193 · Cited by 474 · see citing works
TRPV4 Forms a Novel Ca 2+ Signaling Complex With Ryanodine Receptors and BK Ca Channels
Earley, S., Heppner, T. J., Nelson, M. T., & Brayden, J. E. (2005) · Circulation Research · doi:10.1161/01.res.0000194321.60300.d6 · Cited by 448 · see citing works
Yue, T., Wang, C., Gu, J.-L., Ma, X., Kumar, S., Lee, J. C., Feuerstein, G., Thomas, H. C., Maleeff, B. E., & Ohlstein, E. H. (2000) · Circulation Research · doi:10.1161/01.res.86.6.692 · Cited by 421 · see citing works
Self-citationTransient Receptor Potential Channels in Cardiovascular Function and Disease
Inoue, R., Jensen, L. J., Shi, J., Morita, H., Nishida, M., Honda, A., & Ito, Y. (2006) · Circulation Research · doi:10.1161/01.res.0000233356.10630.8a · Cited by 366 · see citing works
Köhler, R., Heyken, W., Heinau, P., Schubert, R., Si, H., Kacik, M., Busch, C., Grgic, I., Maier, T., & Hoyer, J. D. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000225698.36212.6a · Cited by 346 · see citing works
Transient Receptor Potential Vanilloid 4–Mediated Disruption of the Alveolar Septal Barrier
Alvarez, D. F., KING, J. A. C., Weber, D. S., Addison, E., Liedtke, W., & Townsley, M. I. (2006) · Circulation Research · doi:10.1161/01.res.0000247065.11756.19 · Cited by 311 · see citing works
Yang, X.-R., Lin, M., McIntosh, L. S., & Sham, J. S. K. (2006) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00515.2005 · Cited by 278 · see citing works
Self-citationRecent Developments in Vascular Endothelial Cell Transient Receptor Potential Channels
Yao, X., & Garland, C. J. (2005) · Circulation Research · doi:10.1161/01.res.0000187473.85419.3e · Cited by 272 · see citing works
Ca 2+ Signaling, TRP Channels, and Endothelial Permeability
Tiruppathì, C., Ahmmed, G. U., Vogel, S. M., & Malik, A. B. (2006) · Microcirculation · doi:10.1080/10739680600930347 · Cited by 239 · see citing works
Hamanaka, K., Jian, M., Weber, D. S., Alvarez, D. F., Townsley, M. I., Al‐Mehdi, A. B., KING, J. A. C., Liedtke, W., & Parker, J. C. (2007) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00221.2007 · Cited by 211 · see citing works
TRP channels in endothelial function and dysfunction
Kwan, H. Y., Huang, Y., & Yao, X. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2007.02.013 · Cited by 150 · see citing works
Tian, W., Michele Salanova, A., Xu, H., Lindsley, J. N., Oyama, T., Anderson, S., Bachmann, S., & Cohen, D. (2004) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00397.2003 · Cited by 142 · see citing works
High Vascular Pressure–Induced Lung Injury Requires P450 Epoxygenase–Dependent Activation of TRPV4
Jian, M., KING, J. A. C., Al‐Mehdi, A., Liedtke, W., & Townsley, M. I. (2007) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2007-0192oc · Cited by 139 · see citing works
TRPV4‐mediated regulation of epithelial permeability
Reiter, B., Kraft, R., Günzel, D., Zeißig, S., Schulzke, J., Fromm, M., & Harteneck, C. (2006) · The FASEB Journal · doi:10.1096/fj.06-5772com · Cited by 126 · see citing works
Plant, T., & Strotmann, R. (2007) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-34891-7_11 · Cited by 95 · see citing works
Mallotoxin Is a Novel Human Ether-a-go-go-Related Gene (hERG) Potassium Channel Activator
Zeng, H., Lozinskaya, I. M., Lin, Z., Willette, R. N., Brooks, D. P., & Xu, X. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.110593 · Cited by 76 · see citing works
Self-citationBehm, D. J., Harrison, S. M., Ao, Z., Maniscalco, K., Pickering, S. J., Grau, E., Woods, T. N., Coatney, R. W., Doe, C. P. A., Willette, R. N., et al. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705254 · Cited by 64 · see citing works
Self-citationSulpizio, A. C., Pullen, M. A., Edwards, R. M., Louttit, J. B., West, R., & Brooks, D. P. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.084749 · Cited by 24 · see citing works
Self-citationMolecular Diversity of Receptor Operated Channels in Vascular Smooth Muscle
Earley, S. (2006) · Circulation Research · doi:10.1161/01.res.0000231255.32630.df · Cited by 10 · see citing works
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Elementary Ca <sup>2+</sup> Signals Through Endothelial TRPV4 Channels Regulate Vascular Function
Sonkusare, S. K., Bonev, A. D., Ledoux, J., Liedtke, W., Kotlikoff, M. I., Heppner, T. J., Hill-Eubanks, D. C., & Nelson, M. T. (2012) · Science · doi:10.1126/science.1216283 · Cited by 552 · see citing works
Transient receptor potential channels as therapeutic targets
Moran, M. M., McAlexander, M. A., Bı́ró, T., & SZALLASI, A. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3456 · Cited by 546 · see citing works
Nilius, B., & SZALLASI, A. (2014) · Pharmacological Reviews · doi:10.1124/pr.113.008268 · Cited by 504 · see citing works
TRPV4: molecular conductor of a diverse orchestra
White, J. P. M., Cibelli, M., Urban, L., Nilius, B., McGeown, J. G., & Nagy, I. (2016) · Physiological Reviews · doi:10.1152/physrev.00016.2015 · Cited by 405 · see citing works
Transient Receptor Potential Channels in the Vasculature
Earley, S., & Brayden, J. E. (2015) · Physiological Reviews · doi:10.1152/physrev.00026.2014 · Cited by 414 · see citing works
Pharmacology of Vanilloid Transient Receptor Potential Cation Channels
Vriens, J., Appendino, G., & Nilius, B. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.055624 · Cited by 416 · see citing works
Everaerts, W., Zhen, X.-G., Ghosh, D., Vriens, J., Gevaert, T., Gilbert, J. P., Hayward, N. J., McNamara, C. R., Xue, F., Moran, M. M., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005333107 · Cited by 417 · see citing works
Thorneloe, K. S., Sulpizio, A. C., Lin, Z., Figueroa, D. J., Clouse, A. K., McCafferty, G. P., Chendrimada, T. P., Lashinger, E. S. R., Gordon, E., Evans, L. C., et al. (2008) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.139295 · Cited by 413 · see citing works
Self-citationTransient receptor potential ( TRP ) channels: a clinical perspective
Kaneko, Y., & SZALLASI, A. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12414 · Cited by 373 · see citing works
The vanilloid transient receptor potential channel TRPV4: From structure to disease
Everaerts, W., Nilius, B., & Owsianik, G. (2009) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2009.10.002 · Cited by 347 · see citing works
TRPV4 Is a Regulator of Adipose Oxidative Metabolism, Inflammation, and Energy Homeostasis
Li, Y., Kleiner, S., Wu, J., Sah, R., Gupta, R. K., Banks, A. S., Cohen, P., Khandekar, M. J., Boström, P., Mepani, R. J., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.034 · Cited by 340 · see citing works
TRPV4-mediated endothelial Ca2+ influx and vasodilation in response to shear stress
Mendoza, S. A., Fang, J., Gutterman, D. D., Wilcox, D. A., Bubolz, A. H., Li, R., Suzuki, M., & Zhang, D. X. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00854.2009 · Cited by 342 · see citing works
Thorneloe, K. S., Cheung, M., Bao, W., Alsaid, H., Lenhard, S., Jian, M.-Y., Costell, M., Maniscalco-Hauk, K., Krawiec, J. A., Olzinski, A., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004276 · Cited by 337 · see citing works
Self-citationFélétou, M., & Vanhoutte, P. M. (2009) · Clinical Science · doi:10.1042/cs20090096 · Cited by 331 · see citing works
Calcium‐activated potassium channels and endothelial dysfunction: therapeutic options?
Félétou, M. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00052.x · Cited by 244 · see citing works
Sulk, M., Seeliger, S., Aubert, J., Schwab, V. D., Cevikbas, F., Rivier, M., Nowak, P., Voegel, J. J., Buddenkotte, J., & Steinhoff, M. S. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2011.424 · Cited by 234 · see citing works
TRPV4-dependent dilation of peripheral resistance arteries influences arterial pressure
Earley, S., Pauyo, T., Drapp, R., Tavares, M. J., Liedtke, W., & Brayden, J. E. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00241.2009 · Cited by 232 · see citing works
Ryskamp, D. A., Witkovsky, P., Barabás, P., Huang, W. C., Koehler, C. L., Akimov, N. P., Lee, S. H., Chauhan, S., Xing, W., Renterı́a, R. C., et al. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0359-11.2011 · Cited by 228 · see citing works
TRP Channels as Potential Drug Targets
Moran, M. M. (2017) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010617-052832 · Cited by 218 · see citing works
Balakrishna, S., Song, W., Achanta, S., Doran, S. F., Liu, B., Kaelberer, M. M., Yu, Z., Sui, A., Cheung, M., Leishman, E., et al. (2014) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00065.2014 · Cited by 203 · see citing works
Self-citationTRPV channels and vascular function
Baylie, R. L., & Brayden, J. E. (2010) · Acta Physiologica · doi:10.1111/j.1748-1716.2010.02217.x · Cited by 203 · see citing works
Félétou, M. (2011) · Colloquium Series on Integrated Systems Physiology From Molecule to Function · doi:10.4199/c00031ed1v01y201105isp019 · Cited by 202 · see citing works
Zhang, D. X., Mendoza, S. A., Bubolz, A. H., Mizuno, A., Ge, Z., Li, R., Warltier, D. C., Suzuki, M., & Gutterman, D. D. (2009) · Hypertension · doi:10.1161/hypertensionaha.108.127100 · Cited by 197 · see citing works
Transient receptor potential ( TRP ) channels in the airway: role in airway disease
Grace, M. S., Baxter, M. D., Dubuis, E. D., Birrell, M. A., & Belvisi, M. G. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12538 · Cited by 190 · see citing works
Mechanosensitive TRP channels in cardiovascular pathophysiology
Inoue, R., Zhong, J., & Kawarabayashi, Y. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.05.009 · Cited by 189 · see citing works
Role of TRP channels in the cardiovascular system
Yue, Z., Xie, J., Yu, A. S., Stock, J., Du, J., & Yue, L. (2014) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00457.2014 · Cited by 185 · see citing works
Veldhuis, N. A., Poole, D. P., Grace, M. S., McIntyre, P., & Bunnett, N. W. (2014) · Pharmacological Reviews · doi:10.1124/pr.114.009555 · Cited by 172 · see citing works
TRPV4 and the Regulation of Vascular Tone
Filosa, J. A., Yao, X., & Rath, G. (2012) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e318279ba42 · Cited by 168 · see citing works
Transient receptor potential channelopathies
Nilius, B., & Owsianik, G. (2010) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-010-0788-2 · Cited by 168 · see citing works
García-Elías, A., Mrkonjić, S., Jung, C., Pardo-Pastor, C., Vicente, R., & Valverde, M. A. (2014) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-54215-2_12 · Cited by 161 · see citing works
TRPV4 Agonists and Antagonists
Vincent, F., & Duncton, M. A. J. (2011) · Current Topics in Medicinal Chemistry · doi:10.2174/156802611796904861 · Cited by 154 · see citing works
Ischemic Heart Disease and Heart Failure: Role of Coronary Ion Channels
Severino, P., D’Amato, A., Pucci, M., Infusino, F., Birtolo, L. I., Mariani, M. V., Lavalle, C., Maestrini, V., Mancone, M., & Fedele, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093167 · Cited by 160 · see citing works
Application of the Pentafluorosulfanyl Group as a Bioisosteric Replacement
Sowaileh, M. F., Hazlitt, R. A., & Colby, D. A. (2017) · ChemMedChem · doi:10.1002/cmdc.201700356 · Cited by 151 · see citing works
TRP channels: Emerging targets for respiratory disease
Banner, K. H., Igney, F. H., & Poll, C. T. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.03.005 · Cited by 138 · see citing works
TRPV4—A Missing Link Between Mechanosensation and Immunity
Michalick, L., & Kuebler, W. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00413 · Cited by 139 · see citing works
Negri, S., Faris, P. S., Berra‐Romani, R., Guerra, G., & Moccia, F. D. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2019.01618 · Cited by 132 · see citing works
Modulation of the TRPV4 ion channel as a therapeutic target for disease
Grace, M. S., Bonvini, S. J., Belvisi, M. G., & McIntyre, P. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.019 · Cited by 133 · see citing works
Astrocyte regulation of cerebral vascular tone
Filosa, J. A., & Iddings, J. A. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00359.2013 · Cited by 124 · see citing works
Update on vascular endothelial Ca2+signalling: A tale of ion channels, pumps and transporters
Moccia, F. D. (2012) · World Journal of Biological Chemistry · doi:10.4331/wjbc.v3.i7.127 · Cited by 119 · see citing works
Arresting a Transient Receptor Potential (TRP) Channel
Shukla, A. K., Kim, J., Ahn, S., Xiao, K., Shenoy, S. K., Liedtke, W., & Lefkowitz, R. J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.141549 · Cited by 111 · see citing works
Modulation of water efflux through functional interaction between TRPV4 and TMEM16A/anoctamin 1
Takayama, Y., Shibasaki, K., Suzuki, Y., Yamanaka, A., & Tominaga, M. (2014) · The FASEB Journal · doi:10.1096/fj.13-243436 · Cited by 111 · see citing works
Mihara, H., Boudaka, A., Sugiyama, T., Moriyama, Y., & Tominaga, M. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.207829 · Cited by 110 · see citing works
Bao, W., Aravindhan, K., Alsaid, H., Chendrimada, T. P., Szapacs, M. E., Citerone, D. R., Harpel, M. R., Willette, R. N., Lepore, J. J., & Jucker, B. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023570 · Cited by 105 · see citing works
Self-citationAdapala, R. K., Talasila, P. K., Bratz, I. N., Zhang, D. X., Suzuki, M., Meszaros, J. G., & Thodeti, C. K. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00142.2011 · Cited by 101 · see citing works
Vascular TRP Channels: Performing Under Pressure and Going with the Flow
Hill‐Eubanks, D. C., Gonzales, A. L., Sonkusare, S. K., & Nelson, M. T. (2014) · Physiology · doi:10.1152/physiol.00009.2014 · Cited by 103 · see citing works
Cheung, M., Bao, W., Behm, D. J., Brooks, C. A., Bury, M. J., Dowdell, S. E., Eidam, H. S., Fox, R. M., Goodman, K. B., Holt, D. A., et al. (2017) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.7b00094 · Cited by 99 · see citing works
Self-citationEndothelium-Dependent Hyperpolarization and Endothelial Dysfunction
Félétou, M. (2015) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000346 · Cited by 98 · see citing works
Determinants of TRPV4 Activity following Selective Activation by Small Molecule Agonist GSK1016790A
Jin, M., Wu, Z., Chen, L., Jaimes, J., Collins, D., Walters, E. T., & O’Neil, R. G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016713 · Cited by 98 · see citing works
Gradilone, S. A., Masyuk, T. V., Huang, B. Q., Bañales, J. M., Lehmann, G. L., Radtke, B. N., Stroope, A. J., Masyuk, A. I., Splinter, P. L., & LaRusso, N. F. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.04.010 · Cited by 94 · see citing works
Baxter, M. D., Eltom, S. M., Dekkak, B., Yew‐Booth, L., Dubuis, E. D., Maher, S. A., Belvisi, M. G., & Birrell, M. A. (2014) · Thorax · doi:10.1136/thoraxjnl-2014-205467 · Cited by 95 · see citing works
Zhang, L., Papadopoulos, P., & Hamel, É. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12315 · Cited by 94 · see citing works
Phuong, T. T. T., Redmon, S. N., Yarishkin, O., Winter, J. M., Li, D. Y., & Križaj, D. (2017) · The Journal of Physiology · doi:10.1113/jp275052 · Cited by 91 · see citing works
Facilitation of TRPV4 by TRPV1 is required for itch transmission in some sensory neuron populations
Kim, S., Barry, D. M., Liu, X., Yin, S., Munanairi, A., Meng, Q.-T., Cheng, W., Ping, M., Wan, L., Liu, S.-B., et al. (2016) · Science Signaling · doi:10.1126/scisignal.aaf1047 · Cited by 90 · see citing works
Modulation of TRPV4 by diverse mechanisms
Darby, W. G., Grace, M. S., Baratchi, S., & McIntyre, P. (2016) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2016.07.012 · Cited by 90 · see citing works
Calcium signalling and breast cancer
So, C. L., Saunus, J. M., Roberts‐Thomson, S. J., & Monteith, G. R. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.11.001 · Cited by 88 · see citing works
Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease
Köhler, R., Kaistha, B. P., & Wulff, H. (2010) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728220903540257 · Cited by 85 · see citing works
Oncosis and apoptosis induction by activation of an overexpressed ion channel in breast cancer cells
Peters, A. A., Jamaludin, S. Y. N., Yapa, K. T. D. S., Chalmers, S., Wiegmans, A. P., Lim, H. F., Milevskiy, M. J. G., Azimi, I., Davis, F. M., Northwood, K. S., et al. (2017) · Oncogene · doi:10.1038/onc.2017.234 · Cited by 85 · see citing works
Zhang, D. X., & Gutterman, D. D. (2010) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3181fd35d1 · Cited by 82 · see citing works
Sukumaran, S. V., Singh, T. U., Parida, S., Reddy, C. E. N., Thangamalai, R., Kandasamy, K., Singh, V., & Mishra, S. K. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2013.09.005 · Cited by 81 · see citing works
Role of MMP2 and MMP9 in TRPV4-induced lung injury
Villalta, P. C., Ročić, P., & Townsley, M. I. (2014) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00113.2014 · Cited by 81 · see citing works
Jones, J. L., Peana, D., Veteto, A. B., Lambert, M. D., Nourian, Z., Karasseva, N. G., Hill, M. A., Lindman, B. R., Baines, C. P., Krenz, M., et al. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy156 · Cited by 80 · see citing works
Earley, S. (2010) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3181f580d9 · Cited by 79 · see citing works
TRPV4 Dysfunction Promotes Renal Cystogenesis in Autosomal Recessive Polycystic Kidney Disease
Zaika, O., Mamenko, M., Berrout, J., Boukelmoune, N., O’Neil, R. G., & Pochynyuk, O. M. (2013) · Journal of the American Society of Nephrology · doi:10.1681/asn.2012050442 · Cited by 77 · see citing works
Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling
Thakore, P., & Earley, S. (2019) · Comprehensive physiology · doi:10.1002/cphy.c180034 · Cited by 77 · see citing works
Klausen, T. K., Pagani, A., Minassi, A., Ech‐Chahad, A., Prenen, J., Owsianik, G., Hoffmann, E. K., Pedersen, S. F., Appendino, G., & Nilius, B. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm9001007 · Cited by 74 · see citing works
Kuebler, W. M., Jordt, S., & Liedtke, W. (2020) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00161.2020 · Cited by 73 · see citing works
Ji, C., & McCulloch, C. A. (2020) · FEBS Journal · doi:10.1111/febs.15665 · Cited by 73 · see citing works
TRPV4: physiological role and therapeutic potential in respiratory diseases
Goldenberg, N. M., Ravindran, K., & Kuebler, W. M. (2014) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-014-1058-1 · Cited by 71 · see citing works
Seki, T., Gotō, K., Kiyohara, K., Kansui, Y., Murakami, N., Haga, Y., Ohtsubo, T., Matsumura, K., & Kitazono, T. (2016) · Hypertension · doi:10.1161/hypertensionaha.116.07110 · Cited by 72 · see citing works
Effects of TRPV4 cation channel activation on the primary bladder afferent activities of the rat
Aizawa, N., Wyndaele, J., Homma, Y., & Igawa, Y. (2011) · Neurourology and Urodynamics · doi:10.1002/nau.21212 · Cited by 71 · see citing works
Role of Transient Receptor Potential Vanilloid 4 in Vascular Function
Liu, L., Guo, M., Lv, X., Wang, Z., Yang, J., Li, Y., Yu, F., Wen, X., Feng, L., & Zhou, T. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.677661 · Cited by 70 · see citing works
Dalsgaard, T., Sonkusare, S. K., Teuscher, C., Poynter, M. E., & Nelson, M. T. (2016) · Scientific Reports · doi:10.1038/srep33841 · Cited by 69 · see citing works
Monaghan, K. P., McNaughten, J., McGahon, M. K., Kelly, C., Kyle, D., Yong, P. H., McGeown, J. G., & Curtis, T. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128359 · Cited by 69 · see citing works
Woolums, B. M., McCray, B. A., Sung, H., Tabuchi, M., Sullivan, J. M., Takle, K. A., Yang, Y., Mamah, C., Aisenberg, W. H., Saavedra-Rivera, P. C., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16411-5 · Cited by 68 · see citing works
A novel TRPV4-specific agonist inhibits monocyte adhesion and atherosclerosis
Xu, S., Liu, B., Yin, M., Королева, М. В., Mastrangelo, M. A., Ture, S. K., Morrell, C. N., Zhang, D. X., Fisher, E. A. A., & Jin, Z. G. (2016) · Oncotarget · doi:10.18632/oncotarget.9376 · Cited by 68 · see citing works
Toft‐Bertelsen, T. L., Križaj, D., & MacAulay, N. (2017) · The Journal of Physiology · doi:10.1113/jp274135 · Cited by 68 · see citing works
Calcium signals that determine vascular resistance
Ottolini, M., Hong, K., & Sonkusare, S. K. (2019) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1448 · Cited by 66 · see citing works
Emerging concepts for the role of TRP channels in the cardiovascular system
Vennekens, R. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.202077 · Cited by 61 · see citing works
Vanilloid and Melastatin Transient Receptor Potential Channels in Vascular Smooth Muscle
Earley, S. (2010) · Microcirculation · doi:10.1111/j.1549-8719.2010.00026.x · Cited by 60 · see citing works
Dong, Q., Li, J., Wu, Q., Zhao, N., Qian, C., Ding, D., Wang, B., Chen, L., Guo, K., Fu, D., et al. (2017) · Scientific Reports · doi:10.1038/srep42678 · Cited by 61 · see citing works
Recent advances in TRPV4 agonists and antagonists
Lawhorn, B. G., Brnardic, E. J., & Behm, D. J. (2020) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2020.127022 · Cited by 61 · see citing works
Self-citationBrooks, C. A., Barton, L. S., Behm, D. J., Eidam, H. S., Fox, R. M., Hammond, M., Hoang, T. H., Holt, D. A., Hilfiker, M. A., Lawhorn, B. G., et al. (2019) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.9b00274 · Cited by 59 · see citing works
Self-citationNociceptive and pro‐inflammatory effects of dimethylallyl pyrophosphate via TRPV4 activation
Bang, S., Yoo, S., Yang, T., Cho, H., & Hwang, S. W. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01884.x · Cited by 59 · see citing works
McAlexander, M. A., Luttmann, M. A., Hunsberger, G. E., & Undem, B. J. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.210203 · Cited by 59 · see citing works
Aravindhan, K., Bao, W., Harpel, M. R., Willette, R. N., Lepore, J. J., & Jucker, B. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0130894 · Cited by 60 · see citing works
Self-citationBeyond Hot and Spicy: TRPV Channels and their Pharmacological Modulation
Seebohm, G., & Schreiber, J. A. (2021) · Cellular Physiology and Biochemistry · doi:10.33594/000000358 · Cited by 56 · see citing works
TRPV4 Mechanotransduction in Fibrosis
Adapala, R. K., Katari, V., Teegala, L. R., Thodeti, S., Paruchuri, S. M., & Thodeti, C. K. (2021) · Cells · doi:10.3390/cells10113053 · Cited by 59 · see citing works
Kumar, H., Lim, C. S., Choi, H., Joshi, H. P., Kim, K., Kim, Y. H., Park, C., Kim, H. M., & Han, I. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.2035-19.2020 · Cited by 57 · see citing works
GPCR ‐mediated EGF receptor transactivation regulates TRPV 4 action in the vasculature
Saifeddine, M., El‐Daly, M., Mihara, K., Bunnett, N. W., McIntyre, P., Altier, C., Hollenberg, M. D., & Ramachandran, R. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13072 · Cited by 53 · see citing works
Modulators of Transient Receptor Potential (TRP) Channels as Therapeutic Options in Lung Disease
Dietrich, A. (2019) · Pharmaceuticals · doi:10.3390/ph12010023 · Cited by 54 · see citing works
Genovese, M., Borrelli, A., Venturini, A., Guidone, D., Caci, E., Viscido, G., Gambardella, G., di Bernardo, D., Scudieri, P., & Galietta, L. J. V. (2019) · The Journal of Physiology · doi:10.1113/jp278784 · Cited by 54 · see citing works
Matsumoto, K., Yamaba, R., Inoue, K., Utsumi, D., Tsukahara, T., Amagase, K., Tominaga, M., & Kato, S. (2017) · British Journal of Pharmacology · doi:10.1111/bph.14072 · Cited by 52 · see citing works
Rapid Assessment of Nanoparticle Extravasation in a Microfluidic Tumor Model
Vu, M. N., Rajasekhar, P., Poole, D. P., Khor, S. Y., Truong, N. P., Nowell, C. J., Quinn, J. F., Whittaker, M., Veldhuis, N. A., & Davis, T. P. (2019) · ACS Applied Nano Materials · doi:10.1021/acsanm.8b02056 · Cited by 52 · see citing works
Dragoni, S., Guerra, G., Fiorio, A., Bertoni, G., Rappa, A., Poletto, V., Bottino, C., Aronica, A., Lodola, F., Cinelli, M. P., et al. (2014) · Journal of Cellular Physiology · doi:10.1002/jcp.24686 · Cited by 51 · see citing works
Narita, K., Sasamoto, S., Koizumi, S., Okazaki, S., Nakamura, H., Inoue, T., & Takeda, S. (2015) · The FASEB Journal · doi:10.1096/fj.14-261396 · Cited by 50 · see citing works
TRPV4: a Sensor for Homeostasis and Pathological Events in the CNS
Kumar, H., Lee, S., Kim, K., Zeng, X., & Han, I. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0998-8 · Cited by 50 · see citing works
Deruyver, Y., Weyne, E., Dewulf, K., Rietjens, R., Pinto, S., Ranst, N. V., Franken, J., Vanneste, M., Albersen, M., Gevaert, T., et al. (2018) · European Urology · doi:10.1016/j.eururo.2018.05.020 · Cited by 50 · see citing works
Transient receptor potential vanilloid 1 ( TRPV 1), TRPV 4, and the kidney
Kaßmann, M., Harteneck, C., Zhu, Z., Nürnberg, B., Tepel, M., & Gollasch, M. (2012) · Acta Physiologica · doi:10.1111/apha.12051 · Cited by 49 · see citing works
Oliván‐Viguera, A., García-Otín, A. L., Lozano-Gerona, J., Lachén, E. A., García‐Malinis, A. J., Hamilton, K. L., Gilaberte, Y., Pueyo, E., & Köhler, R. (2018) · PLoS ONE · doi:10.1371/journal.pone.0190307 · Cited by 49 · see citing works
Nayak, P. S., Wang, Y., Najrana, T., Priolo, L., Rios, M., Shaw, S. K., & Sanchez‐Esteban, J. (2015) · Respiratory Research · doi:10.1186/s12931-015-0224-4 · Cited by 48 · see citing works
- Authors
- Willette, R. N., Bao, W., Nerurkar, S., Yue, T.-L., Doe, C. P., Stankus, G., Turner, G. H., Ju, H., Thomas, H., Fishman, C. E., Sulpizio, A., Behm, D. J., Hoffman, S., Lin, Z., Lozinskaya, I., Casillas, L. N., Lin, M., Lee Trout, R. E., Votta, B. J., Thorneloe, K., Lashinger, E. S. R., Figueroa, D. J., Marquis, R., & Xu, X.
- Affiliations
- GlaxoSmithKline (United States) (US)
- ORCID
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 326
- Issue
- 2
- Pages
- 443-452
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2161804336
- Cited by
- 300
- References
- 21
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 8 · 2023: 20 · 2022: 16 · 2021: 14 · 2020: 24 · 2019: 21 · 2018: 16 · 2017: 22 · 2016: 17 · 2015: 19 · 2014: 22 · 2013: 14 · 2012: 20
- FWCI
- 7.46
- Type
- journal article
- Language
- en
- Update notices
- erratum (2011-07-01)
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- TRPV4, GSK1016790A, cardiovascular collapse, endothelial permeability, endothelial injury, endothelial cell retraction, nitric oxide synthase, endothelium-dependent relaxation, blood pressure reduction, cardiac output, TRPV4 knockout mice, edema
- MeSH terms
- Animals, Aorta, Thoracic, Capillary Permeability, Cell Adhesion, Cell Line, Dogs, Dose-Response Relationship, Drug, Endothelium, Vascular, Female, Hemodynamics, Humans, Immunohistochemistry, Leucine, Male, Sulfonamides, Vasoconstriction, Molecular Structure, Ventricular Function, Left, Rats, Sprague-Dawley, Mice, Knockout, Patch-Clamp Techniques, TRPV Cation Channels, Mice, Rats
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