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

Scientific Reports
M KeshavarzG Krasteva-Christ

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-/- intrapul...Continue Reading

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Citations

Feb 25, 2020·Journal of Cachexia, Sarcopenia and Muscle·Dinesh S ShahHarinder S Hundal
Oct 21, 2019·Experimental and Molecular Pathology·Ritu KulshresthaAmteshwar Singh Jaggi

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Methods Mentioned

BETA
co-immunoprecipitation
electron microscopy
PCR
Co-IP
FRET
genotyping
biopsies
immunoprecipitation
electrophoresis

Software Mentioned

GraphPad Prism
image J

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