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Tas2R activation relaxes airway smooth muscle by release of Gα(t) targeting on AChR signaling
Both chronic obstructive pulmonary disease (COPD) and asthma are severe respiratory diseases. Bitter receptor–mediated bronchodilation is a potential therapy for asthma, but the mechanism underlying the agonistic relaxation of airway smooth muscle (ASM) is not well defined. By exploring the ASM rela...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245679/ https://www.ncbi.nlm.nih.gov/pubmed/35737832 http://dx.doi.org/10.1073/pnas.2121513119 |
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author | Zhou, Yu-Wei Sun, Jie Wang, Ye Chen, Cai-Ping Tao, Tao Ma, Ming Chen, Xin Zhang, Xue-Na Yang, Li-Yuan Zhang, Zhong-Liang Li, Ye-Qiong Jiang, Zhi-Hui Qiu, Tian-Tian Wang, Han Pan, Yang Zhang, Jian Chen, Hua-Qun Wang, Pei Zhu, Min-Sheng |
author_facet | Zhou, Yu-Wei Sun, Jie Wang, Ye Chen, Cai-Ping Tao, Tao Ma, Ming Chen, Xin Zhang, Xue-Na Yang, Li-Yuan Zhang, Zhong-Liang Li, Ye-Qiong Jiang, Zhi-Hui Qiu, Tian-Tian Wang, Han Pan, Yang Zhang, Jian Chen, Hua-Qun Wang, Pei Zhu, Min-Sheng |
author_sort | Zhou, Yu-Wei |
collection | PubMed |
description | Both chronic obstructive pulmonary disease (COPD) and asthma are severe respiratory diseases. Bitter receptor–mediated bronchodilation is a potential therapy for asthma, but the mechanism underlying the agonistic relaxation of airway smooth muscle (ASM) is not well defined. By exploring the ASM relaxation mechanism of bitter substances, we observed that pretreatment with the bitter substances nearly abolished the methacholine (MCh)-induced increase in the ASM cell (ASMC) calcium concentration, thereby suppressing the calcium-induced contraction release. The ASM relaxation was significantly inhibited by simultaneous deletion of three Gα(t) proteins, suggesting an interaction between Tas2R and AChR signaling cascades in the relaxation process. Biochemically, the Gα(t) released by Tas2R activation complexes with AChR and blocks the Gα(q) cycling of AChR signal transduction. More importantly, a bitter substance, kudinoside A, not only attenuates airway constriction but also significantly inhibits pulmonary inflammation and tissue remodeling in COPD rats, indicating its modulation of additional Gα(q)-associated pathological processes. Thus, our results suggest that Tas2R activation may be an ideal strategy for halting multiple pathological processes of COPD. |
format | Online Article Text |
id | pubmed-9245679 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-92456792022-12-23 Tas2R activation relaxes airway smooth muscle by release of Gα(t) targeting on AChR signaling Zhou, Yu-Wei Sun, Jie Wang, Ye Chen, Cai-Ping Tao, Tao Ma, Ming Chen, Xin Zhang, Xue-Na Yang, Li-Yuan Zhang, Zhong-Liang Li, Ye-Qiong Jiang, Zhi-Hui Qiu, Tian-Tian Wang, Han Pan, Yang Zhang, Jian Chen, Hua-Qun Wang, Pei Zhu, Min-Sheng Proc Natl Acad Sci U S A Biological Sciences Both chronic obstructive pulmonary disease (COPD) and asthma are severe respiratory diseases. Bitter receptor–mediated bronchodilation is a potential therapy for asthma, but the mechanism underlying the agonistic relaxation of airway smooth muscle (ASM) is not well defined. By exploring the ASM relaxation mechanism of bitter substances, we observed that pretreatment with the bitter substances nearly abolished the methacholine (MCh)-induced increase in the ASM cell (ASMC) calcium concentration, thereby suppressing the calcium-induced contraction release. The ASM relaxation was significantly inhibited by simultaneous deletion of three Gα(t) proteins, suggesting an interaction between Tas2R and AChR signaling cascades in the relaxation process. Biochemically, the Gα(t) released by Tas2R activation complexes with AChR and blocks the Gα(q) cycling of AChR signal transduction. More importantly, a bitter substance, kudinoside A, not only attenuates airway constriction but also significantly inhibits pulmonary inflammation and tissue remodeling in COPD rats, indicating its modulation of additional Gα(q)-associated pathological processes. Thus, our results suggest that Tas2R activation may be an ideal strategy for halting multiple pathological processes of COPD. National Academy of Sciences 2022-06-23 2022-06-28 /pmc/articles/PMC9245679/ /pubmed/35737832 http://dx.doi.org/10.1073/pnas.2121513119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Zhou, Yu-Wei Sun, Jie Wang, Ye Chen, Cai-Ping Tao, Tao Ma, Ming Chen, Xin Zhang, Xue-Na Yang, Li-Yuan Zhang, Zhong-Liang Li, Ye-Qiong Jiang, Zhi-Hui Qiu, Tian-Tian Wang, Han Pan, Yang Zhang, Jian Chen, Hua-Qun Wang, Pei Zhu, Min-Sheng Tas2R activation relaxes airway smooth muscle by release of Gα(t) targeting on AChR signaling |
title | Tas2R activation relaxes airway smooth muscle by release of Gα(t) targeting on AChR signaling |
title_full | Tas2R activation relaxes airway smooth muscle by release of Gα(t) targeting on AChR signaling |
title_fullStr | Tas2R activation relaxes airway smooth muscle by release of Gα(t) targeting on AChR signaling |
title_full_unstemmed | Tas2R activation relaxes airway smooth muscle by release of Gα(t) targeting on AChR signaling |
title_short | Tas2R activation relaxes airway smooth muscle by release of Gα(t) targeting on AChR signaling |
title_sort | tas2r activation relaxes airway smooth muscle by release of gα(t) targeting on achr signaling |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245679/ https://www.ncbi.nlm.nih.gov/pubmed/35737832 http://dx.doi.org/10.1073/pnas.2121513119 |
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