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Nowadays, it is widely known that several kinds of long-acting bronchodilators reduce the frequency of COPD exacerbations. However, limited data are available concerning the complementary additive effects on airflow obstruction. Using an optical method and a selective pH indicator, we succeeded in evaluating the gland secretion rate and the pH in swine tracheal membrane. A physiologically relevant concentration of acetylcholine (ACh) 100\u00a0nM induced a gradual increase in the amount of gland secretion. Lipopolysaccharides (LPS) accelerated the ACh-induced secretory responses up to around threefold and lowered the pH level significantly. Long-acting \u03b2<jats:sub>2<\/jats:sub>-agonists (LABAs) including indacaterol (IND), formoterol, and salmeterol restored the LPS-induced changes in both the hypersecretion and acidification. The subsequent addition of the long-acting muscarine antagonist, glycopyrronium, further increased the pH values. Two different inhibitors for cystic fibrosis transmembrane conductance regulator (CFTR), NPPB and CFTR<jats:sub>inh172<\/jats:sub>, abolished the IND-mediated pH normalization in the presence of both ACh and ACh\u2009+\u2009LPS. Both immunofluorescence staining and western blotting analysis revealed that LPS downregulated the abundant expression of CFTR protein. However, IND did not restore the LPS-induced decrease in CFTR expression on Calu-3 cells. These findings suggest that the activation of cAMP-dependent HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> secretion through CFTR would be partly involved in the IND-mediated pH normalization in gland secretion and may be suitable for the maintenance of airway defense against exacerbating factors including LPS.<\/jats:p>","DOI":"10.1007\/s00424-021-02560-z","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T22:02:36Z","timestamp":1621893756000},"page":"883-896","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of indacaterol on the LPS-evoked changes in fluid secretion rate and pH in swine tracheal membrane"],"prefix":"10.1007","volume":"473","author":[{"given":"Hidemi","family":"Aritake","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0600-0610","authenticated-orcid":false,"given":"Tsutomu","family":"Tamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunichi","family":"Gamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Nara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itsuro","family":"Kazama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Ichinose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisatoshi","family":"Sugiura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"2560_CR1","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.lfs.2016.03.031","volume":"152","author":"G Anzalone","year":"2016","unstructured":"Anzalone G, Gagliardo R, Bucchieri F, Albano GD, Siena L, Montalbano AM, Bonanno A, Riccobono L, Pieper MP, Gjomarkaj M, Profita M (2016) IL-17A induces chromatin remodeling promoting IL-8 release in bronchial epithelial cells: effect of Tiotropium. 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