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Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways

The mechanisms of controlling airway smooth muscle (ASM) tone are of utmost clinical importance as inappropriate constriction is a hallmark in asthma and chronic obstructive pulmonary disease. Receptors for acetylcholine and serotonin, two relevant mediators in this context, appear to be incorporate...

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Autores principales: Keshavarz, M., Skill, M., Hollenhorst, M. I., Maxeiner, S., Walecki, M., Pfeil, U., Kummer, W., Krasteva-Christ, G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951923/
https://www.ncbi.nlm.nih.gov/pubmed/29760450
http://dx.doi.org/10.1038/s41598-018-25445-1
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author Keshavarz, M.
Skill, M.
Hollenhorst, M. I.
Maxeiner, S.
Walecki, M.
Pfeil, U.
Kummer, W.
Krasteva-Christ, G.
author_facet Keshavarz, M.
Skill, M.
Hollenhorst, M. I.
Maxeiner, S.
Walecki, M.
Pfeil, U.
Kummer, W.
Krasteva-Christ, G.
author_sort Keshavarz, M.
collection PubMed
description The mechanisms of controlling airway smooth muscle (ASM) tone are of utmost clinical importance as inappropriate constriction is a hallmark in asthma and chronic obstructive pulmonary disease. Receptors for acetylcholine and serotonin, two relevant mediators in this context, appear to be incorporated in specialized, cholesterol-rich domains of the plasma membrane, termed caveolae due to their invaginated shape. The structural protein caveolin-1 partly accounts for anchoring of these receptors. We here determined the role of the other major caveolar protein, caveolin-3 (cav-3), in orchestrating cholinergic and serotonergic ASM responses, utilizing newly generated cav-3 deficient mice. Cav-3 deficiency fully abrogated serotonin-induced constriction of extrapulmonary airways in organ baths while leaving intrapulmonary airways unaffected, as assessed in precision cut lung slices. The selective expression of cav-3 in tracheal, but not intrapulmonary bronchial epithelial cells, revealed by immunohistochemistry, might explain the differential effects of cav-3 deficiency on serotonergic ASM constriction. The cholinergic response of extrapulmonary airways was not altered, whereas a considerable increase was observed in cav-3(−/−) intrapulmonary bronchi. Thus, cav-3 differentially organizes serotonergic and cholinergic signaling in ASM through mechanisms that are specific for airways of certain caliber and anatomical position. This may allow for selective and site-specific intervention in hyperreactive states.
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spelling pubmed-59519232018-05-21 Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways Keshavarz, M. Skill, M. Hollenhorst, M. I. Maxeiner, S. Walecki, M. Pfeil, U. Kummer, W. Krasteva-Christ, G. Sci Rep Article The mechanisms of controlling airway smooth muscle (ASM) tone are of utmost clinical importance as inappropriate constriction is a hallmark in asthma and chronic obstructive pulmonary disease. Receptors for acetylcholine and serotonin, two relevant mediators in this context, appear to be incorporated in specialized, cholesterol-rich domains of the plasma membrane, termed caveolae due to their invaginated shape. The structural protein caveolin-1 partly accounts for anchoring of these receptors. We here determined the role of the other major caveolar protein, caveolin-3 (cav-3), in orchestrating cholinergic and serotonergic ASM responses, utilizing newly generated cav-3 deficient mice. Cav-3 deficiency fully abrogated serotonin-induced constriction of extrapulmonary airways in organ baths while leaving intrapulmonary airways unaffected, as assessed in precision cut lung slices. The selective expression of cav-3 in tracheal, but not intrapulmonary bronchial epithelial cells, revealed by immunohistochemistry, might explain the differential effects of cav-3 deficiency on serotonergic ASM constriction. The cholinergic response of extrapulmonary airways was not altered, whereas a considerable increase was observed in cav-3(−/−) intrapulmonary bronchi. Thus, cav-3 differentially organizes serotonergic and cholinergic signaling in ASM through mechanisms that are specific for airways of certain caliber and anatomical position. This may allow for selective and site-specific intervention in hyperreactive states. Nature Publishing Group UK 2018-05-14 /pmc/articles/PMC5951923/ /pubmed/29760450 http://dx.doi.org/10.1038/s41598-018-25445-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Keshavarz, M.
Skill, M.
Hollenhorst, M. I.
Maxeiner, S.
Walecki, M.
Pfeil, U.
Kummer, W.
Krasteva-Christ, G.
Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways
title Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways
title_full Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways
title_fullStr Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways
title_full_unstemmed Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways
title_short Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways
title_sort caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951923/
https://www.ncbi.nlm.nih.gov/pubmed/29760450
http://dx.doi.org/10.1038/s41598-018-25445-1
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