TRPA1 is a member of the Transient Receptor Potential (TRP) family of ion channels, and is expressed in sensory nerve endings of the pain pathway. It has been reported that TRPA1 is activated by a variety of noxious stimuli including pungent natural compounds and environmental irritants. However, it has been poorly reported that high-affinity endogenous ligands directly activate TRPA1. Here, we show that 15-deoxy-delta 12,14-Prostaglandin J2 (15d-PGJ2), an endogenous α, β-unsaturated ketone that is produced in inflammation, activates TRPA1. Ca2+ imaging showed that 15d-PGJ2 activates heterologously expressed TRPA1 in HEK293 cells with an apparent EC50 of 890 nM. Site-directed mutagenesis studies and binding assay indicate that cytoplasmic N-terminal cysteines of the channel is involved in 15d-PGJ2 activity on TRPA1. Our results indicate that 15d-PGJ2, an inflammatory compound, may directly activate TRPA1 in nervous system. [J Physiol Sci. 2008;58 Suppl:S78]
