A number of TRPV4 agonists and antagonists have been identified in the past ten years. The discovery of unselective modulators (e.g. antagonist Ruthenium Red) was followed by the apparition of more potent (agonist 4aPDD) or selective (antagonist RN-1734) compounds, including some with bioavailability suitable for in vivo pharmacology studies such as agonist GSK1016790A (with ~10 fold selectivity vs TRPV1) and antagonist HC-067047 (with ~5 fold selectivity vs hERG and ~10 fold selectivity vs TRPM8).
Wolfgang Liedtke, M.D., Ph.D., associate professor of neurology and neurobiology at Duke University School of Medicine reported in the Proceedings of the National Academy of Sciences (PNAS) that studies on genetically engineered mouse model missing TRPV4 only in the cells of the epidermis and on mouse cell cultures have led to the conclusion that exposure to UVB rays caused calcium to flow into the skin cells, but only when the TRPV4 ion channel was present; the influx of calcium ions brings in another molecule called endothelin, which triggers TRPV4 to send more calcium into the cells. Endothelin is known to cause pain and to evoke itching in humans. Could Discovery Lead to End of Sunburn Pain? (Science Daily)
^ abClapham DE, Julius D, Montell C, Schultz G (Dec 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacol Rev57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID16382100.
^Suzuki M, Hirao A, Mizuno A (December 2003). "Microtubule-associated [corrected] protein 7 increases the membrane expression of transient receptor potential vanilloid 4 (TRPV4)". J. Biol. Chem.278 (51): 51448–53. doi:10.1074/jbc.M308212200. PMID14517216.
^Xu, Hongshi; Zhao Hongyu, Tian Wei, Yoshida Kiyotsugu, Roullet Jean-Baptiste, Cohen David M (Mar 2003). "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. (United States) 278 (13): 11520–7. doi:10.1074/jbc.M211061200. ISSN0021-9258. PMID12538589.Cite uses deprecated parameters (help)