| Title: | Species differences in activation of TRPA1 by resin additive-related chemicals relevant to indoor air quality |
| Author(s): | Mori Y; Tanaka-Kagawa T; Tahara M; Kawakami T; Aoki A; Okamoto Y; Isobe T; Ohkawara S; Hanioka N; Azuma K; Sakai S; Jinno H; |
| Address: | "Faculty of Pharmacy, Meijo University. Faculty of Pharmacy, Yokohama University of Pharmacy. Division of Environmental Chemistry, National Institute of Health Sciences. Department of Environmental Medicine and Behavioral Science, Kindai University Faculty of Medicine" |
| ISSN/ISBN: | 1880-3989 (Electronic) 0388-1350 (Linking) |
| Abstract: | "Transient Receptor Potential Ankyrin 1 (TRPA1), which is expressed in the airways, has causative and exacerbating roles in respiratory diseases. TRPA1 is known as a target of sick building syndrome-related air pollutants, such as formaldehyde. Thus, an in vitro TRPA1 activation assay would be useful for predicting the potential risk of air pollution. In this study, we used human TRPA1 (hTRPA1)- and mouse TRPA1 (mTRPA1)-expressing cell lines to measure TRPA1 activation by the emerging indoor air pollutants 2-ethyl-1-hexanol (2-EH), a mixture of 2,2,4-trimethyl-1,3-pentanediol 1- and 3-monoisobutyrate (Texanol), and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). The results indicated that 2-EH activated both hTRPA1 and mTRPA1 in a concentration-dependent manner, whereas TXIB did not activate hTRPA1 or mTRPA1. Texanol also activated hTRPA1 in a concentration-dependent manner. In contrast, a bell-shaped concentration-dependent curve was observed for mouse TRPA1 activation by Texanol, indicating inhibitory effects at a higher concentration range, which was also reported for menthol, a typical TRPA1 modulator. To further elucidate the mechanism underlying the species difference in TRPA1 activation by Texanol, V875G and G878V mutations were introduced into hTRPA1 and mTRPA1, respectively, which were reported to be key mutations for the inhibitory effect of menthol. These mutations switched the inhibitory effects of Texanol; thus, hTRPA1/V875G, but not mTRPA1/G878V, was inhibited at higher concentrations of Texanol. These results indicate that Texanol shares an interaction site with menthol. Overall, these findings suggest that careful interpretation is necessary when extrapolating rodent TRPA1-dependent toxicological effects to humans, especially with respect to the risk assessment of indoor air pollutants" |
| Keywords: | "Humans Mice Animals *Air Pollution, Indoor/adverse effects/analysis Menthol Species Specificity *Air Pollutants/toxicity TRPA1 Cation Channel/genetics Indoor air quality guidelines Nociceptive receptor Transient Receptor Potential Ankyrin 1 Volatile organ;" |
| Notes: | "MedlineMori, Yoko Tanaka-Kagawa, Toshiko Tahara, Maiko Kawakami, Tsuyoshi Aoki, Akira Okamoto, Yoshinori Isobe, Takashi Ohkawara, Susumu Hanioka, Nobumitsu Azuma, Kenichi Sakai, Shinobu Jinno, Hideto eng Japan 2023/01/05 J Toxicol Sci. 2023; 48(1):37-45. doi: 10.2131/jts.48.37" |
