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The first objective of this study was therefore to test whether combined agonist stimulation augments anion transport responses in the Capan-1 monolayer model of human pancreatic duct epithelium. The second objective was to test the influence of H<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>-ATPase inhibition on anion transport in Capan-1 monolayers. The third objective was to analyze the expression and function of K<jats:sup>+<\/jats:sup> channels in Capan-1, which could support anion secretion and cooperate with H<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>-ATPases in pH and potassium homeostasis. The human pancreatic adenocarcinoma cell line Capan-1 was cultured conventionally or as polarized monolayers that were analyzed by Ussing chamber electrophysiological recordings. Single-cell intracellular calcium was assayed with Fura-2. mRNA isolated from Capan-1 was analyzed by use of the nCounter assay or RT-PCR. Protein expression was assessed by immunofluorescence and western blot analyses. Combined stimulation with different physiological agonists enhanced anion transport responses compared to single agonist stimulation. The responsiveness of Capan-1 cells to histamine was also revealed in these experiments. The H<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>-ATPase inhibitor omeprazole reduced carbachol- and riluzole-induced anion transport responses. Transcript analyses revealed abundant TASK-2, TWIK-1, TWIK-2, TASK-5, K<jats:sub>Ca3.1<\/jats:sub>, and KCNQ1 mRNA expression. KCNE1 mRNA and TREK-1, TREK-2, TASK-2, and KCNQ1 protein expression were also shown. This study shows that the Capan-1 model recapitulates key physiological aspects of a bicarbonate-secreting epithelium and constitutes a valuable model for functional studies on human pancreatic duct epithelium.<\/jats:p>","DOI":"10.1007\/s00424-022-02782-9","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T15:02:46Z","timestamp":1671462166000},"page":"361-379","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synergistic effects of agonists and two-pore-domain potassium channels on secretory responses of human pancreatic duct cells Capan-1"],"prefix":"10.1007","volume":"475","author":[{"given":"Christiane E.","family":"S\u00f8rensen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Trauzold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nynne M.","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa","family":"Tawfik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Szczepanowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Novak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,19]]},"reference":[{"issue":"Suppl 1","key":"2782_CR1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1159\/000201523","volume":"58","author":"G Adler","year":"1997","unstructured":"Adler G (1997) Regulation of human pancreatic secretion. 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