Ousingsawat, Jiraporn and Centeio, Raquel and Reyne, Nicole and Mccarron, Alexandra and Cmielewski, Patricia and Schreiber, Rainer and Distefano, Gabriella and Roemermann, Dorothee and Seidler, Ursula and Donnelley, Martin and Kunzelmann, Karl (2024) Inhibition of mucus secretion by niclosamide and benzbromarone in airways and intestine. SCIENTIFIC REPORTS, 14 (1): 1464. ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
The Ca2+ activated Cl- channel TMEM16A (anoctamin 1; ANO1) is expressed in secretory epithelial cells of airways and intestine. Previous studies provided evidence for a role of ANO1 in mucus secretion. In the present study we investigated the effects of the two ANO1-inhibitors niclosamide (Niclo) and benzbromarone (Benz) in vitro and in vivo in mouse models for cystic fibrosis (CF) and asthma. In human CF airway epithelial cells (CFBE), Ca2+ increase and activation of ANO1 by adenosine triphosphate (ATP) or ionomycin was strongly inhibited by 200 nM Niclo and 1 mu M Benz. In asthmatic mice airway mucus secretion was inhibited by intratracheal instillation of Niclo or Benz. In homozygous F508del-cftr mice, intestinal mucus secretion and infiltration by CD45-positive cells was inhibited by intraperitoneal injection of Niclo (13 mg/kg/day for 7 days). In homozygous F508del-cftr rats intestinal mucus secretion was inhibited by oral application of Benz (5 mg/kg/day for 60 days). Taken together, well tolerated therapeutic concentrations of niclosamide and benzbromarone corresponding to plasma levels of treated patients, inhibit ANO1 and intracellular Ca2+ signals and may therefore be useful in inhibiting mucus hypersecretion and mucus obstruction in airways and intestine of patients suffering from asthma and CF, respectively.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CYSTIC-FIBROSIS; ANOCTAMIN 1; TMEM16A; CHANNEL; OVEREXPRESSION; ACTIVATION; EXPRESSION; RELEASE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Sep 2025 09:01 |
| Last Modified: | 15 Sep 2025 09:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64204 |
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