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

Authors :
Kenichi Kato
Tomo Kita
Makoto Tominaga
Yoshiro Suzuki
Kunitoshi Uchida
Jun Yamazaki
Source :
The Journal of Physiological Sciences. 69:305-316
Publication Year :
2018
Publisher :
Springer Science and Business Media LLC, 2018.

Abstract

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.

Details

ISSN :
18806562 and 18806546
Volume :
69
Database :
OpenAIRE
Journal :
The Journal of Physiological Sciences
Accession number :
edsair.doi.dedup.....09525d64a2c80f445da7103126139deb
Full Text :
https://doi.org/10.1007/s12576-018-0647-z