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Bitter Taste Receptors for Asthma Therapeutics

Clinical management of asthma and chronic obstructive pulmonary disease (COPD) has primarily relied on the use of beta 2 adrenergic receptor agonists (bronchodilators) and corticosteroids, and more recently, monoclonal antibody therapies (biologics) targeting specific cytokines and their functions....

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Autores principales: Nayak, Ajay P., Shah, Sushrut D., Michael, James V., Deshpande, Deepak A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647873/
https://www.ncbi.nlm.nih.gov/pubmed/31379597
http://dx.doi.org/10.3389/fphys.2019.00884
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author Nayak, Ajay P.
Shah, Sushrut D.
Michael, James V.
Deshpande, Deepak A.
author_facet Nayak, Ajay P.
Shah, Sushrut D.
Michael, James V.
Deshpande, Deepak A.
author_sort Nayak, Ajay P.
collection PubMed
description Clinical management of asthma and chronic obstructive pulmonary disease (COPD) has primarily relied on the use of beta 2 adrenergic receptor agonists (bronchodilators) and corticosteroids, and more recently, monoclonal antibody therapies (biologics) targeting specific cytokines and their functions. Although these approaches provide relief from exacerbations, questions remain on their long-term efficacy and safety. Furthermore, current therapeutics do not address progressive airway remodeling (AR), a key pathological feature of severe obstructive lung disease. Strikingly, agonists of the bitter taste receptors (TAS2Rs) deliver robust bronchodilation, curtail allergen-induced inflammatory responses in the airways and regulate airway smooth muscle (ASM) cell proliferation and mitigate features of AR in vitro and in animal models. The scope of this review is to provide a comprehensive and systematic insight into our current understanding of TAS2Rs with an emphasis on the molecular events that ensue TAS2R activation in distinct airway cell types and expand on the pleiotropic effects of TAS2R targeting in mitigating various pathological features of obstructive lung diseases. Finally, we will discuss specific opportunities that could help the development of selective agonists for specific TAS2R subtypes in the treatment of asthma.
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spelling pubmed-66478732019-08-02 Bitter Taste Receptors for Asthma Therapeutics Nayak, Ajay P. Shah, Sushrut D. Michael, James V. Deshpande, Deepak A. Front Physiol Physiology Clinical management of asthma and chronic obstructive pulmonary disease (COPD) has primarily relied on the use of beta 2 adrenergic receptor agonists (bronchodilators) and corticosteroids, and more recently, monoclonal antibody therapies (biologics) targeting specific cytokines and their functions. Although these approaches provide relief from exacerbations, questions remain on their long-term efficacy and safety. Furthermore, current therapeutics do not address progressive airway remodeling (AR), a key pathological feature of severe obstructive lung disease. Strikingly, agonists of the bitter taste receptors (TAS2Rs) deliver robust bronchodilation, curtail allergen-induced inflammatory responses in the airways and regulate airway smooth muscle (ASM) cell proliferation and mitigate features of AR in vitro and in animal models. The scope of this review is to provide a comprehensive and systematic insight into our current understanding of TAS2Rs with an emphasis on the molecular events that ensue TAS2R activation in distinct airway cell types and expand on the pleiotropic effects of TAS2R targeting in mitigating various pathological features of obstructive lung diseases. Finally, we will discuss specific opportunities that could help the development of selective agonists for specific TAS2R subtypes in the treatment of asthma. Frontiers Media S.A. 2019-07-16 /pmc/articles/PMC6647873/ /pubmed/31379597 http://dx.doi.org/10.3389/fphys.2019.00884 Text en Copyright © 2019 Nayak, Shah, Michael and Deshpande. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Nayak, Ajay P.
Shah, Sushrut D.
Michael, James V.
Deshpande, Deepak A.
Bitter Taste Receptors for Asthma Therapeutics
title Bitter Taste Receptors for Asthma Therapeutics
title_full Bitter Taste Receptors for Asthma Therapeutics
title_fullStr Bitter Taste Receptors for Asthma Therapeutics
title_full_unstemmed Bitter Taste Receptors for Asthma Therapeutics
title_short Bitter Taste Receptors for Asthma Therapeutics
title_sort bitter taste receptors for asthma therapeutics
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647873/
https://www.ncbi.nlm.nih.gov/pubmed/31379597
http://dx.doi.org/10.3389/fphys.2019.00884
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