Projects per year
Transient receptor potential (TRP) ion channels are important signaling components in nociceptive and inflammatory pathways. This is attributed to their ability to function as polymodal sensors of environmental stimuli (chemical and mechanical) and as effector molecules in receptor signaling pathways. TRP vanilloid 4 (TRPV4) is a nonselective cation channel that is activated by multiple endogenous stimuli including shear stress, membrane stretch, and arachidonic acid metabolites. TRPV4 contributes to many important physiological processes and dysregulation of its activity is associated with chronic conditions of metabolism, inflammation, peripheral neuropathies, musculoskeletal development, and cardiovascular regulation. Mechanosensory and receptor- or lipid-mediated signaling functions of TRPV4 have historically been attributed to central and peripheral neurons. However, with the development of potent and selective pharmacological tools, transgenic mice and improved molecular and imaging techniques, many new roles for TRPV4 have been revealed in nonneuronal cells. In this chapter, we discuss these recent findings and highlight the need for greater characterization of TRPV4-mediated signaling in nonneuronal cell types that are either directly associated with neurons or indirectly control their excitability through release of sensitizing cellular factors. We address the integral role of these cells in sensory and inflammatory processes as well as their importance when considering undesirable on-target effects that may be caused by systemic delivery of TRPV4-selective pharmaceutical agents for treatment of chronic diseases. In future, this will drive a need for targeted drug delivery strategies to regulate such a diverse and promiscuous protein.
|Title of host publication||Ion Channels DownUnder|
|Editors||Dominic P Geraghty, Lachlan D Rash|
|Place of Publication||Cambridge MA USA|
|Number of pages||23|
|Publication status||Published - 2017|
|Name||Advances in Pharmacology|
- Calcium signaling
- Immune cell
- Ion channel
- Transient receptor potential
- 1 Finished
Davis, T., Boyd, B., Bunnett, N., Porter, C., Caruso, F., Kent, S., Thordarson, P., Kearnes, M., Gooding, J., Kavallaris, M., Thurecht, K., Whittaker, A., Parton, R., Corrie, S. R., Johnston, A., McGhee, J., Greguric, I. D., Stevens, M. M., Lewis, J., Lee, D. S., Alexander, C., Dawson, K., Hawker, C., Haddleton, D., Thierry, B., Prestidge, C. A., Meyer, A., Jones-Jayasinghe, N., Voelcker, N. H., Nann, T. & McLean, K.
Australian Research Council (ARC), Monash University, University of Melbourne, University of New South Wales (UNSW), University of Queensland , University of South Australia, Monash University – Internal Faculty Contribution, University of Wisconsin Madison, Memorial Sloan Kettering Cancer Center, University of California System, University College Dublin, Imperial College London, University of Warwick, SungKyunKwan University, Australian Nuclear Science and Technology Organisation (ANSTO) , University of Nottingham
30/06/14 → 29/06/21