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Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity

TRPA1, one of the transient receptor potential channels, has been reported to be involved in nociception and inflammatory pain, suggesting that this molecule could be a promising target for the development of analgesic agents. We screened several monoterpene analogs of camphor, which is known to inh...

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Autores principales: Takaishi, Masayuki, Uchida, Kunitoshi, Fujita, Fumitaka, Tominaga, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Japan 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889502/
https://www.ncbi.nlm.nih.gov/pubmed/24122170
http://dx.doi.org/10.1007/s12576-013-0289-0
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author Takaishi, Masayuki
Uchida, Kunitoshi
Fujita, Fumitaka
Tominaga, Makoto
author_facet Takaishi, Masayuki
Uchida, Kunitoshi
Fujita, Fumitaka
Tominaga, Makoto
author_sort Takaishi, Masayuki
collection PubMed
description TRPA1, one of the transient receptor potential channels, has been reported to be involved in nociception and inflammatory pain, suggesting that this molecule could be a promising target for the development of analgesic agents. We screened several monoterpene analogs of camphor, which is known to inhibit human (h) TRPA1, to identify more effective naturally occurring TRPA1 antagonists. Borneol, 2-methylisoborneol, and fenchyl alcohol exhibited higher inhibitory effects on hTRPA1 activity than either camphor or 1,8-cineole. Our results revealed further that the S873, T874, and Y812 residues of hTRPA1 were involved in the inhibitory effects, suggesting that the hydroxyl group in the six-membered ring of the inhibitors may be interacting with these amino acids. Further research on these identified TRPA1 antagonists could lead to new pain therapeutics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12576-013-0289-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-38895022014-01-14 Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity Takaishi, Masayuki Uchida, Kunitoshi Fujita, Fumitaka Tominaga, Makoto J Physiol Sci Original Paper TRPA1, one of the transient receptor potential channels, has been reported to be involved in nociception and inflammatory pain, suggesting that this molecule could be a promising target for the development of analgesic agents. We screened several monoterpene analogs of camphor, which is known to inhibit human (h) TRPA1, to identify more effective naturally occurring TRPA1 antagonists. Borneol, 2-methylisoborneol, and fenchyl alcohol exhibited higher inhibitory effects on hTRPA1 activity than either camphor or 1,8-cineole. Our results revealed further that the S873, T874, and Y812 residues of hTRPA1 were involved in the inhibitory effects, suggesting that the hydroxyl group in the six-membered ring of the inhibitors may be interacting with these amino acids. Further research on these identified TRPA1 antagonists could lead to new pain therapeutics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12576-013-0289-0) contains supplementary material, which is available to authorized users. Springer Japan 2013-10-12 2014 /pmc/articles/PMC3889502/ /pubmed/24122170 http://dx.doi.org/10.1007/s12576-013-0289-0 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by/2.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Paper
Takaishi, Masayuki
Uchida, Kunitoshi
Fujita, Fumitaka
Tominaga, Makoto
Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity
title Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity
title_full Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity
title_fullStr Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity
title_full_unstemmed Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity
title_short Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity
title_sort inhibitory effects of monoterpenes on human trpa1 and the structural basis of their activity
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889502/
https://www.ncbi.nlm.nih.gov/pubmed/24122170
http://dx.doi.org/10.1007/s12576-013-0289-0
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