TRPV4 agonists and antagonists

Current Topics in Medicinal Chemistry

Volumn 11, Issue 17, 2011, Pages 2216-2226

  Vincent, Fabien ^a   Duncton, Matthew A J ^b  

^a PFIZER INC   (United States)

^b EVOTEC AG   (Germany)

Author keywords

4 PDD; Activator; Blocker; GSK1016790A; Inhibitor; Phorbol ester; RN 1734; RN 1747; Ruthenium red

Indexed keywords

4ALPHA PHORBOL DIDECANOATE; 5,6 EPOXY 8,11,14 ICOSATRIENOIC ACID; BISANDROGRAPHOLIDE A; CAPSAZEPINE; CITRAL; GSK 1016790A; GSK 205; RN 1734; RN 1747; RN 9893; RUTHENIUM RED; TRANSIENT RECEPTOR POTENTIAL CHANNEL; TRANSIENT RECEPTOR POTENTIAL CHANNEL A1; TRANSIENT RECEPTOR POTENTIAL CHANNEL M8; UNCLASSIFIED DRUG; VANILLOID RECEPTOR 1; VANILLOID RECEPTOR 3; VANILLOID RECEPTOR 4; VANILLOID RECEPTOR 4 AGONIST; VANILLOID RECEPTOR 4 ANTAGONIST; VANILLOID RECEPTOR AGONIST; VANILLOID RECEPTOR ANTAGONIST;

BLADDER DYSFUNCTION; BLOOD VESSEL; CELL DIFFERENTIATION; DRUG EFFICACY; DRUG INDICATION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG TARGETING; HUMAN; INFLAMMATORY DISEASE; KERATINOCYTE; KNOCKOUT MOUSE; NEUROPATHIC PAIN; NONHUMAN; OSMOLARITY; OSTEOCLAST; PROTEIN FAMILY; RECEPTOR UPREGULATION; REVIEW; SHEAR STRESS; SKIN TEMPERATURE; STRUCTURE ACTIVITY RELATION; TISSUE DISTRIBUTION; VENTILATOR INDUCED LUNG INJURY;

ANIMALS; DRUG DISCOVERY; HUMANS; MOLECULAR STRUCTURE; MOLECULAR WEIGHT; STRUCTURE-ACTIVITY RELATIONSHIP; TRPV CATION CHANNELS;

EID: 80052228545     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/156802611796904861     Document Type: Review

References (102)

1. Damann, N.; Voets, T.; Nilius, B. TRPs in our senses. Curr. Biol.,2008, 18, R880-889.
2. Venkatachalam, K.; Montell, C. TRP channels. Annu. Rev. Bio-chem., 2007, 76, 387-417.
3. Vennekens, R.; Owsianik, G.; Nilius, B. Vanilloid transient recep-tor potential cation channels: an overview. Curr. Pharm. Des., 2008, 14, 18-31.
4. Caterina, M. J.; Schumacher, M. A.; Tominaga, M.; Rosen, T. A.; Levine, J. D.; Julius, D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature, 1997, 389, 816-824.
5. Cortright, D. N.; Szallasi, A. Biochemical pharmacology of the vanilloid receptor TRPV1. An update. Eur. J. Biochem., 2004, 271, 1814-1819.
6. Szallasi, A.; Cortright, D. N.; Blum, C. A.; Eid, S. R. The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept. Nat. Rev. Drug Discov., 2007, 6, 357-372.
7. Nilius, B.; Vriens, J.; Prenen, J.; Droogmans, G.; Voets, T. TRPV4 calcium entry channel: a paradigm for gating diversity. Am. J. Physiol. Cell Physiol., 2004, 286, C195-C205.
8. Plant, T. D.; Strotmann, R. Trpv4. Handb. Exp. Pharmacol., 2007,189-205.
9. Shigematsu, H.; Sokabe, T.; Danev, R.; Tominaga, M.; Nagayama, K. A 3.5-nm structure of rat TRPV4 cation channel revealed by zernike phase-contrast cryo-EM. J. Biol. Chem., 2009, 285(15),11210-11218.
10. Everaerts, W.; Nilius, B.; Owsianik, G. The vallinoid transient receptor potential channel Trpv4: From structure to disease. Prog. Biophys. Mol. Biol., 2009, 103(1),2-17
11. Liedtke, W.; Friedman, J. M. Abnormal osmotic regulation in trpv4-/- mice. Proc. Natl. Acad. Sci. USA, 2003, 100, 13698-13703.
12. Strotmann, R.; Harteneck, C.; Nunnenmacher, K.; Schultz, G.; Plant, T. D. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat. Cell Biol., 2000, 2, 695-702.
13. Liedtke, W.; Choe, Y.; Marti-Renom, M. A.; Bell, A. M.; Denis, C. S.; Sali, A.; Hudspeth, A. J.; Friedman, J. M.; Heller, S. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell, 2000, 103, 525-535.
14. Guler, A. D.; Lee, H.; Iida, T.; Shimizu, I.; Tominaga, M.; Caterina, M. Heat-evoked activation of the ion channel, TRPV4. J. Neurosci., 2002, 22, 6408-6414.
15. Xu, H.; Zhao, H.; Tian, W.; Yoshida, K.; Roullet, J. B.; Cohen, D. M. Regulation of a transient receptor potential (TRP) channel by tyrosine phosphorylation. SRC family kinase-dependent tyrosine phosphorylation of TRPV4 on TYR-253 mediates its response to hypotonic stress. J. Biol. Chem., 2003, 278, 11520-11527.
16. Fan, H. C.; Zhang, X.; McNaughton, P. A. Activation of the TRPV4 ion channel is enhanced by phosphorylation. J. Biol. Chem., 2009, 284, 27884-27891.
17. Peng, H.; Lewandrowski, U.; Muller, B.; Sickmann, A.; Walz, G.; Wegierski, T. Identification of a Protein Kinase C-dependent phos-phorylation site involved in sensitization of TRPV4 channel. Bio-chem. Biophys. Res. Commun., 2010, 391, 1721-1725.
18. Vriens, J.; Owsianik, G.; Fisslthaler, B.; Suzuki, M.; Janssens, A.; Voets, T.; Morisseau, C.; Hammock, B. D.; Fleming, I.; Busse, R.; Nilius, B. Modulation of the Ca2 permeable cation channel TRPV4 by cytochrome P450 epoxygenases in vascular endothelium. Circ. Res., 2005, 97, 908-915.
19. Watanabe, H.; Vriens, J.; Prenen, J.; Droogmans, G.; Voets, T.; Nilius, B. Anandamide and arachidonic acid use epoxyeicosa-trienoic acids to activate TRPV4 channels. Nature, 2003, 424, 434-438.
20. Chung, M. K.; Lee, H.; Caterina, M. J. Warm temperatures activate TRPV4 in mouse 308 keratinocytes. J. Biol. Chem., 2003, 278, 32037-32046.
21. Fernandez-Fernandez, J. M.; Nobles, M.; Currid, A.; Vazquez, E.; Valverde, M. A. Maxi K channel mediates regulatory volume decrease response in a human bronchial epithelial cell line. Am. J. Physiol. Cell Physiol., 2002, 283, C1705-1714.
22. Jia, Y.; Wang, X.; Varty, L.; Rizzo, C. A.; Yang, R.; Correll, C. C.; Phelps, P. T.; Egan, R. W.; Hey, J. A. Functional TRPV4 channels are expressed in human airway smooth muscle cells. Am. J. Physiol. Lung Cell Mol. Physiol., 2004, 287, L272-278.
23. Wissenbach, U.; Bodding, M.; Freichel, M.; Flockerzi, V. Trp12, a novel Trp related protein from kidney. FEBS Lett., 2000, 485, 127-134.
24. Delany, N. S.; Hurle, M.; Facer, P.; Alnadaf, T.; Plumpton, C.; Kinghorn, I.; See, C. G.; Costigan, M.; Anand, P.; Woolf, C. J.; Crowther, D.; Sanseau, P.; Tate, S. N. Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2. Physiol. Genomics, 2001, 4, 165-174.
25. Birder, L.; Kullmann, F. A.; Lee, H.; Barrick, S.; de Groat, W.; Kanai, A.; Caterina, M. Activation of urothelial transient receptor potential vanilloid 4 by 4alpha-phorbol 12,13-didecanoate contributes to altered bladder reflexes in the rat. J. Pharmacol. Exp. Ther., 2007, 323, 227-235.
26. Gevaert, T.; Vriens, J.; Segal, A.; Everaerts, W.; Roskams, T.; Talavera, K.; Owsianik, G.; Liedtke, W.; Daelemans, D.; Dewa-chter, I.; Van Leuven, F.; Voets, T.; De Ridder, D.; Nilius, B. Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J. Clin. Invest., 2007, 117, 3453-3462.
27. Shen, J.; Harada, N.; Kubo, N.; Liu, B.; Mizuno, A.; Suzuki, M.; Yamashita, T. Functional expression of transient receptor potential vanilloid 4 in the mouse cochlea. Neuroreport, 2006, 17, 135-139.
28. Mizuno, A.; Matsumoto, N.; Imai, M.; Suzuki, M. Impaired osmotic sensation in mice lacking TRPV4. Am. J. Physiol. Cell Physiol., 2003, 285, C96-C101.
29. Shibasaki, K.; Suzuki, M.; Mizuno, A.; Tominaga, M. Effects of body temperature on neural activity in the hippocampus: regulation of resting membrane potentials by transient receptor potential vanilloid 4. J. Neurosci., 2007, 27, 1566-1575.
30. Zhang, Y.; Wang, Y. H.; Ge, H. Y.; Arendt-Nielsen, L.; Wang, R.; Yue, S. W. A transient receptor potential vanilloid 4 contributes to mechanical allodynia following chronic compression of dorsal root ganglion in rats. Neurosci. Lett., 2008, 432, 222-227.
31. Alessandri-Haber, N.; Yeh, J. J.; Boyd, A. E.; Parada, C. A.; Chen, X.; Reichling, D. B.; Levine, J. D. Hypotonicity induces TRPV4-mediated nociception in rat. Neuron, 2003, 39, 497-511.
32. Alessandri-Haber, N.; Dina, O. A.; Yeh, J. J.; Parada, C. A.; Reich-ling, D. B.; Levine, J. D. Transient receptor potential vanilloid 4 is essential in chemotherapy-induced neuropathic pain in the rat. J. Neurosci., 2004, 24, 4444-4452.
33. Wu, L.; Gao, X.; Brown, R. C.; Heller, S.; O'Neil, R. G. Dual role of the TRPV4 channel as a sensor of flow and osmolality in renal epithelial cells. Am. J. Physiol. Renal Physiol., 2007, 293, F1699-1713.
34. Watanabe, H.; Vriens, J.; Suh, S. H.; Benham, C. D.; Droogmans, G.; Nilius, B. Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothe-lial cells. J. Biol. Chem., 2002, 277, 47044-47051.
35. Kohler, R.; Heyken, W. T.; Heinau, P.; Schubert, R.; Si, H.; Kacik, M.; Busch, C.; Grgic, I.; Maier, T.; Hoyer, J. Evidence for a functional role of endothelial transient receptor potential V4 in shear stress-induced vasodilatation. Arterioscler. Thromb. Vasc. Biol., 2006, 26, 1495-1502.
36. Kumar, S.; Pratta, M. A.; Votta, B. J. WO2006029209. Chem. Abstr., 2009, 144, 286221.
37. Masuyama, R.; Vriens, J.; Voets, T.; Karashima, Y.; Owsianik, G.; Vennekens, R.; Lieben, L.; Torrekens, S.; Moermans, K.; Vanden Bosch, A.; Bouillon, R.; Nilius, B.; Carmeliet, G. TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts. Cell Metab., 2008, 8, 257-265.
38. Mizoguchi, F.; Mizuno, A.; Hayata, T.; Nakashima, K.; Heller, S.; Ushida, T.; Sokabe, M.; Miyasaka, N.; Suzuki, M.; Ezura, Y.; Noda, M. Transient receptor potential vanilloid 4 deficiency suppresses unloading-induced bone loss. J. Cell Physiol., 2008, 216, 47-53.
39. 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.; Trout, R. E.; Votta, B. J.; Thorneloe, K.; Lashinger, E. S.; Figueroa, D. J.; Marquis, R.; Xu, X. Systemic activation of the transient receptor potential vanilloid subtype 4 channel causes endothelial failure and circulatory collapse: Part 2. J. Pharmacol. Exp. Ther., 2008, 326, 443-452.
40. Thorneloe, K. S.; Sulpizio, A. C.; Lin, Z.; Figueroa, D. J.; Clouse, A. K.; McCafferty, G. P.; Chendrimada, T. P.; Lashinger, E. S.; Gordon, E.; Evans, L.; Misajet, B. A.; Demarini, D. J.; Nation, J. H.; Casillas, L. N.; Marquis, R. W.; Votta, B. J.; Sheardown, S. A.; Xu, X.; Brooks, D. P.; Laping, N. J.; Westfall, T. D. N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropa noyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamid e (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. J. Pharmacol. Exp. Ther., 2008, 326, 432-442.
41. Suzuki, M.; Mizuno, A.; Kodaira, K.; Imai, M. Impaired pressure sensation in mice lacking TRPV4. J. Biol. Chem., 2003, 278, 22664-22668.
42. Rock, M. J.; Prenen, J.; Funari, V. A.; Funari, T. L.; Merriman, B.; Nelson, S. F.; Lachman, R. S.; Wilcox, W. R.; Reyno, S.; Quadrelli, R.; Vaglio, A.; Owsianik, G.; Janssens, A.; Voets, T.; Ikegawa, S.; Nagai, T.; Rimoin, D. L.; Nilius, B.; Cohn, D. H. Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia. Nat. Genet., 2008, 40, 999-1003.
43. Krakow, D.; Vriens, J.; Camacho, N.; Luong, P.; Deixler, H.; Fu-nari, T. L.; Bacino, C. A.; Irons, M. B.; Holm, I. A.; Sadler, L.; Okenfuss, E. B.; Janssens, A.; Voets, T.; Rimoin, D. L.; Lachman, R. S.; Nilius, B.; Cohn, D. H. Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphy-seal dysplasia, Kozlowski type and metatropic dysplasia. Am. J. Hum. Genet., 2009, 84, 307-315.
44. Nilius, B.; Owsianik, G. Channelopathies converge on TRPV4. Nat. Genet., 2010, 42, 98-100.
45. Liedtke, W. TRPV4 as osmosensor: a transgenic approach. Pflugers Arch., 2005, 451, 176-180.
46. Lowry, C. A.; Lightman, S. L.; Nutt, D. J. That warm fuzzy feeling: brain serotonergic neurons and the regulation of emotion. J. Psychopharmacol., 2009, 23, 392-400.
47. Muramatsu, S.; Wakabayashi, M.; Ohno, T.; Amano, K.; Ooishi, R.; Sugahara, T.; Shiojiri, S.; Tashiro, K.; Suzuki, Y.; Nishimura, R.; Kuhara, S.; Sugano, S.; Yoneda, T.; Matsuda, A. Functional gene screening system identified TRPV4 as a regulator of chondro-genic differentiation. J. Biol. Chem., 2007, 282, 32158-32167.
48. Gao, X.; Wu, L.; O'Neil, R. G. Temperature-modulated diversity of TRPV4 channel gating: activation by physical stresses and phorbol ester derivatives through protein kinase C-dependent and -independent pathways. J. Biol. Chem., 2003, 278, 27129-27137.
49. Landoure, G.; Zdebik, A. A.; Martinez, T. L.; Burnett, B. G.; Stanescu, H. C.; Inada, H.; Shi, Y.; Taye, A. A.; Kong, L.; Munns, C. H.; Choo, S. S.; Phelps, C. B.; Paudel, R.; Houlden, H.; Ludlow, C. L.; Caterina, M. J.; Gaudet, R.; Kleta, R.; Fischbeck, K. H.; Sumner, C. J. Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C. Nat. Genet., 2010, 42, 170-174.
50. Deng, H. X.; Klein, C. J.; Yan, J.; Shi, Y.; Wu, Y.; Fecto, F.; Yau, H. J.; Yang, Y.; Zhai, H.; Siddique, N.; Hedley-Whyte, E. T.; De-long, R.; Martina, M.; Dyck, P. J.; Siddique, T. Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4. Nat. Genet.,2010, 42, 165-169.
51. Auer-Grumbach, M.; Olschewski, A.; Papic, L.; Kremer, H.; McEntagart, M. E.; Uhrig, S.; Fischer, C.; Frohlich, E.; Balint, Z.; Tang, B.; Strohmaier, H.; Lochmuller, H.; Schlotter-Weigel, B.; Senderek, J.; Krebs, A.; Dick, K. J.; Petty, R.; Longman, C.; Anderson, N. E.; Padberg, G. W.; Schelhaas, H. J.; van Ravenswaaij-Arts, C. M.; Pieber, T. R.; Crosby, A. H.; Guelly, C. Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapu-loperoneal SMA and HMSN2C. Nat. Genet., 2010, 42, 160-164.
52. Cenac, N.; Altier, C.; Chapman, K.; Liedtke, W.; Zamponi, G.; Vergnolle, N. Transient receptor potential vanilloid-4 has a major role in visceral hypersensitivity symptoms. Gastroenterology, 2008, 135, 937-946, 946 e931-932.
53. Alessandri-Haber, N.; Dina, O. A.; Joseph, E. K.; Reichling, D. B.; Levine, J. D. Interaction of transient receptor potential vanilloid 4, integrin, and SRC tyrosine kinase in mechanical hyperalgesia. J. Neurosci., 2008, 28, 1046-1057.
54. Levine, J. D.; Alessandri-Haber, N. TRP channels: targets for the relief of pain. Biochim. Biophys. Acta 2007, 1772, 989-1003.
55. Grant, A. D.; Cottrell, G. S.; Amadesi, S.; Trevisani, M.; Nicoletti, P.; Materazzi, S.; Altier, C.; Cenac, N.; Zamponi, G. W.; Bautista-Cruz, F.; Lopez, C. B.; Joseph, E. K.; Levine, J. D.; Liedtke, W.; Vanner, S.; Vergnolle, N.; Geppetti, P.; Bunnett, N. W. Protease-activated receptor 2 sensitizes the transient receptor potential vanil-loid 4 ion channel to cause mechanical hyperalgesia in mice. J. Physiol., 2007, 578, 715-733.
56. Alessandri-Haber, N.; Dina, O. A.; Joseph, E. K.; Reichling, D.; Levine, J. D. A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators. J. Neurosci., 2006, 26, 3864-3874.
57. Xu, X.; Gordon, E.; Lin, Z.; Lozinskaya, I. M.; Chen, Y.; Thor-neloe, K. S. Functional TRPV4 channels and an absence of cap-saicin-evoked currents in freshly-isolated, guinea-pig urothelial cells. Channels, (Austin) 2009, 3, 156-160.
58. Alvarez, D. F.; King, J. A.; Weber, D.; Addison, E.; Liedtke, W.; Townsley, M. I. Transient receptor potential vanilloid 4-mediated disruption of the alveolar septal barrier: a novel mechanism of acute lung injury. Circ. Res., 2006, 99, 988-995.
59. Hamanaka, K.; Jian, M. Y.; Townsley, M. I.; King, J. A.; Liedtke, W.; Weber, D. S.; Eyal, F. G.; Clapp, M. M.; Parker, J. C. TRPV4 channels augment macrophage activation and ventilator-induced lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol., 2010, 299, L353-362.
60. Hamanaka, K.; Jian, M. Y.; Weber, D. S.; Alvarez, D. F.; Townsley, M. I.; Al-Mehdi, A. B.; King, J. A.; Liedtke, W.; Parker, J. C. TRPV4 initiates the acute calcium-dependent permeability increase during ventilator-induced lung injury in isolated mouse lungs. Am. J. Physiol. Lung Cell. Mol. Physiol., 2007, 293, L923-932.
61. Watanabe, H.; Davis, J. B.; Smart, D.; Jerman, J. C.; Smith, G. D.; Hayes, P.; Vriens, J.; Cairns, W.; Wissenbach, U.; Prenen, J.; Flockerzi, V.; Droogmans, G.; Benham, C. D.; Nilius, B. Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. J. Biol. Chem., 2002, 277, 13569-13577.
62. Szallasi, A.; Blumberg, P. M. Resiniferatoxin, a phorbol-related diterpene, acts as an ultrapotent analog of capsaicin, the irritant constituent in red pepper. Neuroscience, 1989, 30, 515-520.
63. Vriens, J.; Owsianik, G.; Janssens, A.; Voets, T.; Nilius, B. Determinants of 4 alpha-phorbol sensitivity in transmembrane domains 3 and 4 of the cation channel TRPV4. J. Biol. Chem., 2007, 282, 12796-12803.
64. Ding, X. L.; Wang, Y. H.; Ning, L. P.; Zhang, Y.; Ge, H. Y.; Jiang, H.; Wang, R.; Yue, S. W. Involvement of TRPV4-NO-cGMP-PKG pathways in the development of thermal hyperalgesia following chronic compression of the dorsal root ganglion in rats. Behav. Brain Res., 2010, 208, 194-201.
65. Alessandri-Haber, N.; Dina, O. A.; Chen, X.; Levine, J. D. TRPC1 and TRPC6 channels cooperate with TRPV4 to mediate mechanical hyperalgesia and nociceptor sensitization. J. Neurosci., 2009, 29, 6217-6228.
66. Tsushima, H.; Mori, M. Antidipsogenic effects of a TRPV4 agonist, 4alpha-phorbol 12,13-didecanoate, injected into the cerebrov-entricle. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2006, 290, R1736-1741.
67. Gao, F.; Sui, D.; Garavito, R. M.; Worden, R. M.; Wang, D. H. Salt intake augments hypotensive effects of transient receptor potential vanilloid 4: functional significance and implication. Hypertension, 2009, 53, 228-235.
68. Gao, F.; Wang, D. H. Hypotension induced by activation of the transient receptor potential vanilloid 4 channels: role of Ca2+-activated K+ channels and sensory nerves. J. Hypertens, 2010, 28, 102-110.
69. Vincent, F.; Acevedo, A.; Nguyen, M. T.; Dourado, M.; DeFalco, J.; Gustafson, A.; Spiro, P.; Emerling, D. E.; Kelly, M. G.; Dunc-ton, M. A. Identification and characterization of novel TRPV4 modulators. Biochem. Biophys. Res. Commun., 2009, 389, 490-494.
70. Klausen, T. K.; Pagani, A.; Minassi, A.; Ech-Chahad, A.; Prenen, J.; Owsianik, G.; Hoffmann, E. K.; Pedersen, S. F.; Appendino, G.; Nilius, B. Modulation of the Transient Receptor Potential Vanilloid Channel TRPV4 by 4alpha-Phorbol Esters: A Structure-Activity Study. J. Med. Chem., 2009, 52, 2933-2939.
71. Smith, P. L.; Maloney, K. N.; Pothen, R. G.; Clardy, J.; Clapham, D. E. Bisandrographolide from Andrographis paniculata activates TRPV4 channels. J. Biol. Chem., 2006, 281, 29897-29904.
72. Zygmunt, P. M.; Petersson, J.; Andersson, D. A.; Chuang, H.; Sorgard, M.; Di Marzo, V.; Julius, D.; Hogestatt, E. D. Vanilloid receptors on sensory nerves mediate the vasodilator action of anan-damide. Nature, 1999, 400, 452-457.
73. Marquis, R. W. WO2007098393. Chem. Abstr., 2009, 147, 301493.
74. Jeong, J. U.; Marquis, R. W. WO2007030761. Chem. Abstr., 2009, 146, 338169.
75. Cichy-Knight, M.; Dunn, A. K.; Marquis, R. W. WO2006105475. Chem. Abstr. 2009, 145, 397528.
76. Casillas, L. N.; Marquis, R. W. WO2007070865. Chem. Abstr., 2009, 147, 95915.
77. Casillas, L. N.; Marquis, R. W. WO2007082262. Chem. Abstr., 2009, 147, 166620.
78. Casillas, L. N. J., C.; Marquis, R. W. WO2006029154. Chem. Abstr., 2009, 144, 292584.
79. Casillas, L. N.; Jeong, J. U.; Marquis, R. W. WO2006029210. Chem. Abstr., 2009, 144, 311900.
80. Jeong, J. U. R., A.; Chen, X.; Casillas, L.; Lin, M.; Trout, R.; Lu-engo, J. I.; Lipshutz, D. B.; Votta, B.; Kulkarni, S. G.; Brown, B. S.; Rominger, D.; Yamashita, D. S.; Marquis, R. W. In 238th ACS National Meeting, Washington, DC, United States, August 16-20, 2009; Washington, DC, United States, 2009; MEDI-392.
81. Casillas, L. T., R.; Lin, M.; Rominger, D.; Donovan, B.; Brown, B. S.; Kulkarni, S. G.; Lipshutz, D. B.; Sanjay, K.; Votta, B.; Luengo, J. I.; Marquis, R. In 238th ACS National Meeting, Washington, DC, United States, August 16-20, 2009; Washington, DC, United States, 2009; MEDI-451.
82. Wei, Z.-L. N., M. T.; Acevedo, A.; Zipfel, S.; Defalco, J.; Dourado, M.; Gustafson, A. E.; Steiger, D.; Chi, C.; Yip, V.; Zhang, Q.; Victoria, C. L.; Reubish, D. S.; Spiro, P. A.; Kelly, M. G.; Kincaid, J.; Emerling, D. E.; Duncton, M.; Vincent, F. In Discovery of a Proof-of-Concept TRPV4 antagonist, Keystone Symposia on the Transient Receptor Potential Ion Channel Superfamily, Brecken-ridge, Colorado, USA 2007; Breckenridge, Colorado, USA 2007.
83. Alexander, S. P.; Mathie, A.; Peters, J. A. Guide to Receptors and Channels (GRAC), 3rd edition. Br. J. Pharmacol., 2008, 153 (Suppl 2), 1-209.
84. Michels, G.; Khan, I. F.; Endres-Becker, J.; Rottlaender, D.; Her-zig, S.; Ruhparwar, A.; Wahlers, T.; Hoppe, U. C. Regulation of the human cardiac mitochondrial Ca2+ uptake by 2 different voltage-gated Ca2+ channels. Circulation 2009, 119, 2435-2443.
85. Cibulsky, S. M.; Sather, W. A. Block by ruthenium red of cloned neuronal voltage-gated calcium channels. J. Pharmacol. Exp. Ther., 1999, 289, 1447-1453.
86. Pottosin, II; Dobrovinskaya, O. R.; Muniz, J. Cooperative block of the plant endomembrane ion channel by ruthenium red. Biophys. J., 1999, 77, 1973-1979.
87. Cardoso, C. M.; De Meis, L. Modulation by fatty acids of Ca2+ fluxes in sarcoplasmic-reticulum vesicles. Biochem. J., 1993, 296 (Pt 1), 49-52.
88. Kannurpatti, S. S.; Joshi, P. G.; Joshi, N. B. Calcium sequestering ability of mitochondria modulates influx of calcium through gluta-mate receptor channel. Neurochem. Res., 2000, 25, 1527-1536.
89. Deinum, J.; Wallin, M.; Jensen, P. W. The binding of Ruthenium red to tubulin. Biochim. Biophys. Acta, 1985, 838, 197-205.
90. Yamada, A.; Sato, O.; Watanabe, M.; Walsh, M. P.; Ogawa, Y.; Imaizumi, Y. Inhibition of smooth-muscle myosin-light-chain phosphatase by Ruthenium Red. Biochem. J., 2000, 349 Pt 3, 797-804.
91. Sasaki, T.; Naka, M.; Nakamura, F.; Tanaka, T. Ruthenium red inhibits the binding of calcium to calmodulin required for enzyme activation. J. Biol. Chem., 1992, 267, 21518-21523.
92. Stotz, S. C.; Vriens, J.; Martyn, D.; Clardy, J.; Clapham, D. E. Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons. PLoS One, 2008, 3, e2082.
93. Phan, M. N.; Leddy, H. A.; Votta, B. J.; Kumar, S.; Levy, D. S.; Lipshutz, D. B.; Lee, S. H.; Liedtke, W.; Guilak, F. Functional characterization of TRPV4 as an osmotically sensitive ion channel in porcine articular chondrocytes. Arthritis Rheum., 2009, 60, 3028-3037.
94. Skogvall, S.; Berglund, M.; Dalence-Guzman, M. F.; Svensson, K.; Jonsson, P.; Persson, C. G.; Sterner, O. Effects of capsazepine on human small airway responsiveness unravel a novel class of bron-chorelaxants. Pulm. Pharmacol. Ther., 2007, 20, 273-280.
95. Cheung, M.; Du, Z.; Eidam, H. S.; Fox, R. M. WO2009111680. Chem. Abstr., 2009, 151, 359104.
96. Cheung, M.; Eidam, H. S.; Fox, R. M.; Manas, E. S. WO2009146177. Chem. Abstr., 2009, 152, 27388.
97. Cheung, M.; Eidam, H. S.; Fox, R. M.; Manas, E. S. WO2009146182. Chem. Abstr., 2009, 152, 27389.
98. Cheung, M.; Eidam, H. S. WO2010011912. Chem. Abstr. 2010, 152, 215581.
99. Bury, M. J.; Cheung, M.; Eidam, H. S.; Fox, R. M.; Goodman, K.; Manas, E. S. WO2010011914. Chem. Abstr., 2010, 152, 192445.
100. Tsukamoto, S.; Sawamura, S. JP2009084290. Chem. Abstr., 2009, 150, 438732.
101. Weil, A.; Moore, S. E.; Waite, N. J.; Randall, A.; Gunthorpe, M. J. Conservation of functional and pharmacological properties in the distantly related temperature sensors TRVP1 and TRPM8. Mol. Pharmacol., 2005, 68, 518-527.
102. Everaerts, W.; Zhen, X.; Ghosh, D.; Vriens, J.; Gevaert, T.; Gilbert, J. P.; Hayward, N. J.; McNamara, C. R.; Xue, F.; Moran, M. M.; Strassmaier, T.; Uykal, E.; Owsianik, G.; Vennekens, R.; De Rid-der, D.; Nilius, B.; Fanger, C. M.; Voets, T. Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis. Proc. Natl. Acad. Sci. USA, 2010, 107,19084-19089.