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

Abstract 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 in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	M. Keshavarz, M. Skill, M. I. Hollenhorst, S. Maxeiner, M. Walecki, U. Pfeil, W. Kummer, G. Krasteva-Christ
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/54cf6a93ee4748b8b2025a506fa41d88
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:54cf6a93ee4748b8b2025a506fa41d88
record_format	dspace
spelling	oai:doaj.org-article:54cf6a93ee4748b8b2025a506fa41d882021-12-02T15:08:16ZCaveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways10.1038/s41598-018-25445-12045-2322https://doaj.org/article/54cf6a93ee4748b8b2025a506fa41d882018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25445-1https://doaj.org/toc/2045-2322Abstract 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.M. KeshavarzM. SkillM. I. HollenhorstS. MaxeinerM. WaleckiU. PfeilW. KummerG. Krasteva-ChristNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-18 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q M. Keshavarz M. Skill M. I. Hollenhorst S. Maxeiner M. Walecki U. Pfeil W. Kummer G. Krasteva-Christ Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways
description	Abstract 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.
format	article
author	M. Keshavarz M. Skill M. I. Hollenhorst S. Maxeiner M. Walecki U. Pfeil W. Kummer G. Krasteva-Christ
author_facet	M. Keshavarz M. Skill M. I. Hollenhorst S. Maxeiner M. Walecki U. Pfeil W. Kummer G. Krasteva-Christ
author_sort	M. Keshavarz
title	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_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_sort	caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/54cf6a93ee4748b8b2025a506fa41d88
work_keys_str_mv	AT mkeshavarz caveolin3differentiallyorchestratescholinergicandserotonergicconstrictionofmurineairways AT mskill caveolin3differentiallyorchestratescholinergicandserotonergicconstrictionofmurineairways AT mihollenhorst caveolin3differentiallyorchestratescholinergicandserotonergicconstrictionofmurineairways AT smaxeiner caveolin3differentiallyorchestratescholinergicandserotonergicconstrictionofmurineairways AT mwalecki caveolin3differentiallyorchestratescholinergicandserotonergicconstrictionofmurineairways AT upfeil caveolin3differentiallyorchestratescholinergicandserotonergicconstrictionofmurineairways AT wkummer caveolin3differentiallyorchestratescholinergicandserotonergicconstrictionofmurineairways AT gkrastevachrist caveolin3differentiallyorchestratescholinergicandserotonergicconstrictionofmurineairways
_version_	1718388185478725632

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

Ejemplares similares