Potentiating TMEM16A does not stimulate airway mucus secretion or bronchial and pulmonary arterial smooth muscle contraction.pdf (1.61 MB)
Potentiating TMEM16A does not stimulate airway mucus secretion or bronchial and pulmonary arterial smooth muscle contraction
journal contribution
posted on 2023-06-10, 04:30 authored by H Danahay, Roy FoxRoy Fox, Sarah LilleySarah Lilley, H Charlton, K Adley, L Christie, E Ansari, C Ehre, A Flen, M J Tuvim, B F Dickey, C Williams, S Beaudoin, S P Collingwood, Martin GoslingThe calcium-activated chloride channel (CaCC) TMEM16A enables chloride secretion across several transporting epithelia, including in the airways. Additional roles for TMEM16A have been proposed, which include regulating mucus production and secretion and stimulating smooth muscle contraction. The aim of the present study was to test whether the pharmacological regulation of TMEM16A channel function, could affect any of these proposed biological roles in the airways. In vitro, neither a potent and selective TMEM16A potentiator (ETX001) nor the potent TMEM16A inhibitor (Ani9) influenced either baseline mucin release or goblet cell numbers in well-differentiated primary human bronchial epithelial (HBE) cells. In vivo, a TMEM16A potentiator was without effect on goblet cell emptying in an IL-13 stimulated goblet cell metaplasia model. Using freshly isolated human bronchi and pulmonary arteries, neither ETX001 or Ani9 had any effect on the contractile or relaxant responses of the tissues. In vivo, ETX001 also failed to influence either lung or cardiovascular function when delivered directly into the airways of telemetered rats. Together, these studies do not support a role for TMEM16A in the regulation of goblet cell numbers or baseline mucin release, or on the regulation of airway or pulmonary artery smooth muscle contraction.
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Publication status
- Published
File Version
- Published version
Journal
FASEB BioAdvancesISSN
2573-9832Publisher
WileyExternal DOI
Volume
2Page range
464-477Event location
United StatesDepartment affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2022-08-24First Open Access (FOA) Date
2022-08-24First Compliant Deposit (FCD) Date
2022-08-24Usage metrics
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