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Sci Rep. 2018 May 14;8(1):7508. doi: 10.1038/s41598-018-25445-1.

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

Author information

1
Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Giessen, Germany.
2
Institute of Anatomy and Cell Biology, School of Medicine, Saarland University, Saarbrucken, Germany.
3
German Center for Lung Research (DZL), Marburg, Germany.
4
Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Giessen, Germany. gabriela.krasteva-christ@uks.eu.
5
German Center for Lung Research (DZL), Marburg, Germany. gabriela.krasteva-christ@uks.eu.
6
Institute of Anatomy and Cell Biology, School of Medicine, Saarland University, Saarbrucken, Germany. gabriela.krasteva-christ@uks.eu.

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.

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