FK506 (tacrolimus) causes pain sensation through the activation of transient receptor potential ankyrin 1 (TRPA1) channels

The journal of physiological sciences

article

Tomo Kita¹  Kunitoshi Uchida¹  Kenichi Kato¹  Yoshiro Suzuki²  Makoto Tominaga²  Jun Yamazaki¹ 

[1] Department of Physiological Science and Molecular Biology, Fukuoka Dental College;Division of Cell Signaling, National Institute for Physiological Sciences, National Institutes of Natural Sciences;Thermal Biology Group, Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences

关键词: FK506;    Pain;    TRPA1;    Sensory neuron;    Adverse effect;   

DOI  :  10.1007/s12576-018-0647-z

来源: Springer

【 摘 要 】

FK506 (tacrolimus) is an immunosuppressant widely used as an ointment in the treatment of atopic dermatitis. However, local application of FK506 can evoke burning sensations in atopic dermatitis patients, and its mechanisms are unknown. In this study, we found that FK506 activates transient receptor potential ankyrin 1 (TRPA1) channels. In Ca2+-imaging experiments, increases in intracellular Ca2+ concentrations ([Ca2+]i) by FK506 were observed in HEK293T cells expressing hTRPA1 or hTRPM8. FK506-induced currents were observed in HEK293T cells expressing hTRPA1 or mTRPA1, but less or not at all in cells expressing hTRPV1 or hTRPM8 using a patch-clamp technique. FK506 also evoked single-channel opening of hTRPA1 in an inside-out configuration. FK506-induced [Ca2+]i increases were also observed in TRPA1-expressing mouse primary sensory neurons. Furthermore, injection of FK506 evoked licking or biting behaviors and these behaviors were almost abolished in TRPA1 knockout mice. These results indicate that FK506 might cause pain sensations through TRPA1 activation.

【 授权许可】

Unknown