Activation of Transient Receptor Potential Ankyrin 1 by Eugenol

Abstract

The structural similarity of eugenol to cinnamaldehyde, an active ligand for transient receptor potential ankyrin 1 (TRPA1), suggests that eugenol might produce its effect via TRPA1 in addition to TRPV1 as we reported previously. In this study, I investigated effect of eugenol on TRPA1, by Fura-2-based calcium imaging and whole-cell patch clamp recording in trigeminal ganglion neurons and in a heterologous expression system. As the results, eugenol induced robust calcium responses in rat trigeminal ganglion neurons that responded to a specific TRPA1 agonist, allylisothiocyanate (AITC), but not to capsaicin. Capsazepine, a TRPV1 specific antagonist failed to inhibit eugenol-induced calcium responses in AITC responding neurons. In addition, eugenol response was observed in trigeminal ganglion neurons from TRPV1 knockout mice, which was inhibited by TRPA1-specific antagonist HC-030031. Lastly, involvement of TRPA1 in action of eugenol was confirmed by calcium imaging and patch clamp experiments using human embryonic kidney 293 cells that stably express TRPA1. In summary, these results demonstrate that activation of TRPA1 might account for another molecular mechanism underlying pharmacological action of eugenol.