Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the TRPV4gene. The TRPV4 gene encodes TRPV4, initially named "vanilloid-receptor related osmotically activated channel" and "OSM9-like transient receptor potential channel, member 4 ", a member of the vanilloid subfamily in the transient receptor potential superfamily of ion channels. The encoded protein is a Ca2+-permeable, nonselective cation channel that has been found involved in multiple physiologic functions, dysfunctions and also disease. It functions in the regulation of systemic osmotic pressure by the brain, in vascular function, in liver, intestinal, renal and bladder function, in skin barrier function and response of the skin to ultraviolet-B radiation, in growth and structural integrity of the skeleton, in function of joints, in airway- and lung function, in retinal and inner ear function, and in pain. The channel is activated by osmotic, mechanical and chemical cues. It also responds to thermal changes. Channel activation can be sensitized by inflammation and injury. The TRPV4 gene has been co-discovered by W. Liedtke et al. and R. Strotmann et al.
A number of TRPV4 agonists and antagonists have been identified since its discovery. The discovery of unselective modulators was followed by the apparition of more potent or selective compounds, including some with bioavailability suitable for in vivo pharmacology studies such as agonist GSK1016790A, and antagonists HC-067047 and RN-9893. Resolvin D1, a metabolite of the omega 3 fatty acid, docosahexaenoic acid, is a member of the specialized proresolving mediators class of metabolites that function to resolve diverse inflammatory reactions and diseases in animal models and, it is proposed, humans. This SPM also dampens pain perception arising from various inflammation-based causes in animal models. The mechanism behind this pain-dampening effect involves the inhibition of TRPV4, probably by an indirect effect wherein it activates another receptor located on neurons or nearby microglia or astrocytes. CMKLR1, GPR32, FPR2, and NMDA receptors have been proposed to be the receptors through which a SPM may operate to down-regulate TRPs and thereby pain perception.
