Molecular basis of TRPA1 regulation in nociceptive neurons. A Review.

摘要

Transient receptor potential A1 (TRPA1) is an excitatory ionchannel that functions as a cellular sensor, detecting a widerange of proalgesic agents such as environmental irritants andendogenous products of inflammation and oxidative stress.Topical application of TRPA1 agonists produces an acutenociceptive response through peripheral release ofneuropeptides, purines and other transmitters from activatedsensory nerve endings. This, in turn, further regulates TRPA1activity downstream of G-protein and phospholipase C-coupledsignaling cascades. Despite the important physiological relevanceof such regulation leading to nociceptor sensitization andconsequent pain hypersensitivity, the specific domains throughwhich TRPA1 undergoes post-translational modifications thataffect its activation properties are yet to be determined ata molecular level. This review aims at providing an account ofour current knowledge on molecular basis of regulation byneuronal inflammatory signaling pathways that converge on theTRPA1 channel protein and through modification of its specificresidues influence the extent to which this channel maycontribute to pain.