scholarly journals Sphingomyelinase decreases transepithelial anion secretion in airway epithelial cells in part by inhibiting CFTR‐mediated apical conductance

2021 ◽  
Vol 9 (15) ◽  
Author(s):  
Kirsten A. Cottrill ◽  
Raven J. Peterson ◽  
Colby F. Lewallen ◽  
Michael Koval ◽  
Robert J. Bridges ◽  
...  

2016 ◽  
Vol 310 (1) ◽  
pp. L50-L58 ◽  
Author(s):  
Elizabeth R. Peitzman ◽  
Nathan A. Zaidman ◽  
Peter J. Maniak ◽  
Scott M. O'Grady

Carvedilol functions as a nonselective β-adrenergic receptor (AR)/α1-AR antagonist that is used for treatment of hypertension and heart failure. Carvedilol has been shown to function as an inverse agonist, inhibiting G protein activation while stimulating β-arrestin-dependent signaling and inducing receptor desensitization. In the present study, short-circuit current ( Isc) measurements using human airway epithelial cells revealed that, unlike β-AR agonists, which increase Isc, carvedilol decreases basal and 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate-stimulated current. The decrease in Isc resulted from inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR). The carvedilol effect was abolished by pretreatment with the β2-AR antagonist ICI-118551, but not the β1-AR antagonist atenolol or the α1-AR antagonist prazosin, indicating that its inhibitory effect on Isc was mediated through interactions with apical β2-ARs. However, the carvedilol effect was blocked by pretreatment with the microtubule-disrupting compound nocodazole. Furthermore, immunocytochemistry experiments and measurements of apical CFTR expression by Western blot analysis of biotinylated membranes revealed a decrease in the level of CFTR protein in monolayers treated with carvedilol but no significant change in monolayers treated with epinephrine. These results demonstrate that carvedilol binding to apical β2-ARs inhibited CFTR current and transepithelial anion secretion by a mechanism involving a decrease in channel expression in the apical membrane.



Pneumologie ◽  
2015 ◽  
Vol 69 (07) ◽  
Author(s):  
S Ulrich ◽  
S Weinreich ◽  
R Haller ◽  
S Menke ◽  
R Olmer ◽  
...  


Pneumologie ◽  
2018 ◽  
Vol 72 (S 01) ◽  
pp. S100-S101
Author(s):  
R Lehmann ◽  
M Müller ◽  
TE Klassert ◽  
D Driesch ◽  
M Stock ◽  
...  


2010 ◽  
Vol 243 (3) ◽  
pp. 315-322 ◽  
Author(s):  
Aida Ibricevic ◽  
Steven L. Brody ◽  
Wiley J. Youngs ◽  
Carolyn L. Cannon


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