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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
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.
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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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