Inhibition of ATP hydrolysis restores airway surface liquid production in cystic fibrosis airway epithelia.

Inhibition of ATP hydrolysis restores airway surface liquid production in cystic fibrosis airway epithelia. Am J Physiol Lung Cell Mol Physiol. 2019 Dec 04;: Authors: van Heusden C, Button B, Anderson WH, Ceppe A, Morton LC, O'Neal WK, Dang H, Alexis NE, Donaldson SH, Stephan H, Boucher RC, Lazarowski ER Abstract Airway surface dehydration is a pathological feature of cystic fibrosis (CF) lung disease. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR), a cyclic AMP-regulated Cl- channel controlled in part by the adenosine A2B receptor. An alternative, CFTR-independent mechanism of fluid secretion is regulated by ATP, via the P2Y2 receptor (P2Y2R) that activates Ca2+-regulated Cl- channels (CaCC/TMEM16) and inhibits Na+ absorption. However, due to rapid ATP hydrolysis, steady-state ATP levels in CF airway surface liquid (ASL) are inadequate to maintain P2Y2R-mediated fluid secretion. Therefore, inhibiting airway epithelial ecto-ATPases to increase ASL ATP levels constitutes a strategy to restore airway surface hydration in CF. Using [γ32P]ATP as radiotracer, we assessed the effect of a series of ATPase inhibitory compounds on the stability of physiologically occurring ATP concentrations. We identified the polyoxometalate [Co4(H2O)2(PW9O34)2]10- (POM-5) as the most potent and effective ecto-ATPase inhibitor in CF airway epithelial cells. POM-5 caused long-lasting inhibition of ATP hydrolysis in airway epithelia, which was...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

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PMID: 31977412 [PubMed - in process]
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No abstract available
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Source: Journal of Pediatric Gastroenterology and Nutrition - Category: Gastroenterology Tags: Original Articles: Gastroenterology Source Type: research
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