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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Obstruction / genetics*
  • Airway Obstruction / metabolism
  • Animals
  • Bronchi / metabolism*
  • Caveolin 3 / genetics*
  • Caveolin 3 / metabolism*
  • Constriction, Pathologic
  • Male
  • Mice
  • Mice, Knockout
  • Muscarine / pharmacology
  • Muscle Contraction / drug effects
  • Muscle, Smooth / metabolism
  • Receptors, Cholinergic / metabolism
  • Receptors, Serotonin / metabolism
  • Serotonin / pharmacology
  • Trachea / metabolism*


  • Cav3 protein, mouse
  • Caveolin 3
  • Receptors, Cholinergic
  • Receptors, Serotonin
  • Serotonin
  • Muscarine