Identification of the molecular target of crotamiton, an anti–itch agent

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  • Kittaka Hiroki
    Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute forPhysiological Sciences), National Institutes of Natural Sciences
  • Yamanoi Yu
    Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute forPhysiological Sciences), National Institutes of Natural Sciences Department of Physiological Sciences, the Graduate University for Advanced Studies (SOKENDAI) Research Laboratory, Ikedamohando Co., Ltd.
  • Tominaga Makoto
    Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute forPhysiological Sciences), National Institutes of Natural Sciences Department of Physiological Sciences, the Graduate University for Advanced Studies (SOKENDAI) Institute for Environmental and Gender–Specific Medicine, Juntendo University

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  • 鎮痒剤クロタミトンの標的分子の同定および作用メカニズムの解明

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<p>Crotamiton (N–ethyl–o–crotonotoluidide) has long been used as an anti–itch agent. However, the mechanism by which crotamiton exerts anti–itch effects is unknown. Based on recent studies showing that transient receptor potential (TRP) channels are involved in itch sensations, we hypothesized that crotamiton could affect the activity of TRP channels. In this study, we found that crotamiton strongly inhibits TRPV (vanilloid) 4 channel activity. Crotamiton also inhibited itch–related behaviors induced by the TRPV4–selective agonist GSK1016790A. In patch–clamp experiments we observed large TRPV4 currents following crotamiton washout. In this washout current, single–channel open probabilities and unitary current amplitudes of TRPV4 were increased, which together were suggestive of TRPV4 pore dilation. To explore whether TRPV4 pore dilation occurred, we performed cation replacement experiments in which whole–cell currents and reversal potentials were measured. Our observa­tion of increased cation influx and changes in reversal potentials upon crotami­ton washout indicated the presence of TRPV4 pore dilation. These results identified TRPV4 as a molecular target of crotamiton and demonstrated pore dilation of TRPV4 upon crotamiton washout.</p>

Journal

  • PAIN RESEARCH

    PAIN RESEARCH 33 (1), 47-57, 2018-03-30

    JAPANESE ASSOCIATION FOR STUDY OF PAIN

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