Browse by author
Lookup NU author(s): Livia Delpiano, Dr Michael Gray
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. The solute carrier 26 family member A9 (SLC26A9) is an epithelial anion transporter that is assumed to contribute to airway chloride secretion and surface hydration. Whether SLC26A9 or CFTR is responsible for airway Cl- transport under basal conditions is still unclear, due to the lack of a specific inhibitor for SLC26A9. In the present study, we report a novel potent and specific inhibitor for SLC26A9, identified by screening of a drug-like molecule library and subsequent chemical modifications. The most potent compound S9-A13 inhibited SLC26A9 with an IC50 of 90.9 ± 13.4 nM. S9-A13 did not inhibit other members of the SLC26 family and had no effects on Cl- channels such as CFTR, TMEM16A, or VRAC. S9-A13 inhibited SLC26A9 Cl- currents in cells that lack expression of CFTR. It also inhibited proton secretion by HGT-1 human gastric cells. In contrast, S9-A13 had minimal effects on ion transport in human airway epithelia and mouse trachea, despite clear expression of SLC26A9 in the apical membrane of ciliated cells. In both tissues, basal and stimulated Cl- secretion was due to CFTR, while acidification of airway surface liquid by S9-A13 suggests a role of SLC26A9 for airway bicarbonate secretion.
Author(s): Jo S, Centeio R, Park J, Ousingsawat J, Jeon D-K, Talbi K, Schreiber R, Ryu K, Kahlenberg K, Somoza V, Delpiano L, Gray MA, Amaral MD, Railean V, Beekman JM, Rodenburg LW, Namkung W, Kunzelmann K
Publication type: Article
Publication status: Published
Journal: FASEB Journal
Year: 2022
Volume: 36
Issue: 11
Print publication date: 01/11/2022
Online publication date: 02/10/2022
Acceptance date: 24/08/2022
Date deposited: 31/10/2022
ISSN (print): 0892-6638
ISSN (electronic): 1530-6860
Publisher: John Wiley & Sons Ltd
URL: https://doi.org/10.1096/fj.202200313RR
DOI: 10.1096/fj.202200313RR
PubMed id: 36183361
Altmetrics provided by Altmetric