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Bitter taste receptors on airway smooth muscle bronchodilate by a localized calcium flux and reverse obstruction
Bitter taste receptors (TAS2Rs) of the tongue likely evolved to evoke signals for avoiding ingestion of plant toxins. We found expression of TAS2Rs on human airway smooth muscle (ASM) and considered these to be avoidance receptors for inhalants, leading to ASM contraction and bronchospasm. TAS2R ago...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3066567/ https://www.ncbi.nlm.nih.gov/pubmed/20972434 http://dx.doi.org/10.1038/nm.2237 |
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author | Deshpande, Deepak A Wang, Wayne C H McIlmoyle, Elizabeth L Robinett, Kathryn S Schillinger, Rachel M An, Steven S Sham, James S K Liggett, Stephen B |
author_facet | Deshpande, Deepak A Wang, Wayne C H McIlmoyle, Elizabeth L Robinett, Kathryn S Schillinger, Rachel M An, Steven S Sham, James S K Liggett, Stephen B |
author_sort | Deshpande, Deepak A |
collection | PubMed |
description | Bitter taste receptors (TAS2Rs) of the tongue likely evolved to evoke signals for avoiding ingestion of plant toxins. We found expression of TAS2Rs on human airway smooth muscle (ASM) and considered these to be avoidance receptors for inhalants, leading to ASM contraction and bronchospasm. TAS2R agonists such as saccharin, chloroquine and denatonium evoked increased ASM [Ca(2+)](i) in a Gβγ, PLCβ and IP(3)-receptor dependent manner which would be expected (like acetylcholine) to evoke contraction. Paradoxically, bitter tastants caused relaxation of isolated ASM, and dilation of airways that was 3-fold greater than β-agonists. Relaxation by TAS2Rs is from a localized [Ca(2+)](i) response at the cell membrane which opens BK(Ca) channels leading to ASM membrane hyperpolarization. Inhaled bitter tastants decreased airway obstruction in an asthma mouse model. Given the need for efficacious bronchodilators for treating obstructive lung diseases, this pathway can be exploited for therapy with the thousands of known synthetic and naturally occurring bitter tastants. |
format | Text |
id | pubmed-3066567 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
record_format | MEDLINE/PubMed |
spelling | pubmed-30665672011-05-01 Bitter taste receptors on airway smooth muscle bronchodilate by a localized calcium flux and reverse obstruction Deshpande, Deepak A Wang, Wayne C H McIlmoyle, Elizabeth L Robinett, Kathryn S Schillinger, Rachel M An, Steven S Sham, James S K Liggett, Stephen B Nat Med Article Bitter taste receptors (TAS2Rs) of the tongue likely evolved to evoke signals for avoiding ingestion of plant toxins. We found expression of TAS2Rs on human airway smooth muscle (ASM) and considered these to be avoidance receptors for inhalants, leading to ASM contraction and bronchospasm. TAS2R agonists such as saccharin, chloroquine and denatonium evoked increased ASM [Ca(2+)](i) in a Gβγ, PLCβ and IP(3)-receptor dependent manner which would be expected (like acetylcholine) to evoke contraction. Paradoxically, bitter tastants caused relaxation of isolated ASM, and dilation of airways that was 3-fold greater than β-agonists. Relaxation by TAS2Rs is from a localized [Ca(2+)](i) response at the cell membrane which opens BK(Ca) channels leading to ASM membrane hyperpolarization. Inhaled bitter tastants decreased airway obstruction in an asthma mouse model. Given the need for efficacious bronchodilators for treating obstructive lung diseases, this pathway can be exploited for therapy with the thousands of known synthetic and naturally occurring bitter tastants. 2010-10-24 2010-11 /pmc/articles/PMC3066567/ /pubmed/20972434 http://dx.doi.org/10.1038/nm.2237 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Deshpande, Deepak A Wang, Wayne C H McIlmoyle, Elizabeth L Robinett, Kathryn S Schillinger, Rachel M An, Steven S Sham, James S K Liggett, Stephen B Bitter taste receptors on airway smooth muscle bronchodilate by a localized calcium flux and reverse obstruction |
title | Bitter taste receptors on airway smooth muscle bronchodilate by a localized calcium flux and reverse obstruction |
title_full | Bitter taste receptors on airway smooth muscle bronchodilate by a localized calcium flux and reverse obstruction |
title_fullStr | Bitter taste receptors on airway smooth muscle bronchodilate by a localized calcium flux and reverse obstruction |
title_full_unstemmed | Bitter taste receptors on airway smooth muscle bronchodilate by a localized calcium flux and reverse obstruction |
title_short | Bitter taste receptors on airway smooth muscle bronchodilate by a localized calcium flux and reverse obstruction |
title_sort | bitter taste receptors on airway smooth muscle bronchodilate by a localized calcium flux and reverse obstruction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3066567/ https://www.ncbi.nlm.nih.gov/pubmed/20972434 http://dx.doi.org/10.1038/nm.2237 |
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