{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:28:25Z","timestamp":1788492505993,"version":"build-2803163510"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Research Council of Thailand-Mahidol University"},{"DOI":"10.13039\/501100004192","name":"National Science and Technology Development Agency","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004192","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Thailand Science Research and Innovation (TSRI)-Mahidol University"},{"name":"TSRI-Burapha University"},{"name":"TRF-Royal Golden Jubilee Ph.D. Program","award":["PHD\/0105\/2557"],"award-info":[{"award-number":["PHD\/0105\/2557"]}]},{"DOI":"10.13039\/501100007180","name":"Faculty of Science, Mahidol University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007180","id-type":"DOI","asserted-by":"crossref"}]},{"name":"MU-MiniRC Grant from Mahidol University)"},{"name":"TRF\/TSRI-International Research Network Program","award":["IRN60W0001"],"award-info":[{"award-number":["IRN60W0001"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Vasoactive intestinal peptide (VIP) as a neurocrine factor released by enteric neurons has been postulated to participate in the regulation of transcellular active calcium transport across intestinal epithelium, but the preceding evidence is scant and inconclusive. Herein, transepithelial calcium flux and epithelial electrical parameters were determined by Ussing chamber technique with radioactive tracer in the intestinal epithelium-like Caco-2 monolayer grown on Snapwell. After 3-day culture, Caco-2 cells expressed mRNA of calcium transporters, i.e., TRPV6, calbindin-D<jats:sub>9k<\/jats:sub>, PMCA<jats:sub>1b<\/jats:sub> and NCX1, and exhibited transepithelial resistance of ~200 \u03a9 cm<jats:sup>2<\/jats:sup>, a characteristic of leaky epithelium similar to the small intestine. VIP receptor agonist was able to enhance transcellular calcium flux, whereas VIP receptor antagonist totally abolished calcium fluxes induced by 1,25-dihydroxyvitamin D<jats:sub>3<\/jats:sub> [1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>]. Since the intestinal cystic fibrosis transmembrane conductance regulator (CFTR) could be activated by VIP and calciotropic hormones, particularly parathyroid hormone, we sought to determine whether CFTR also contributed to the 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>-induced calcium transport. A selective CFTR inhibitor (20\u2013200 \u03bcM CFTR<jats:sub>inh<\/jats:sub>-172) appeared to diminish calcium fluxes as well as transepithelial potential difference and short-circuit current, both of which indicated a decrease in electrogenic ion transport. On the other hand, 50 \u03bcM genistein\u2014a molecule that could rapidly activate CFTR\u2014was found to increase calcium transport. Our <jats:italic>in silico<\/jats:italic> molecular docking analysis confirmed direct binding of CFTR<jats:sub>inh<\/jats:sub>-172 and genistein to CFTR channels. In conclusion, VIP and CFTR apparently contributed to the intestinal calcium transport, especially in the presence of 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>, thereby supporting the existence of the neurocrine control of intestinal calcium absorption.<\/jats:p>","DOI":"10.1371\/journal.pone.0277096","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T18:29:49Z","timestamp":1668796189000},"page":"e0277096","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Vasoactive intestinal peptide and cystic fibrosis transmembrane conductance regulator contribute to the transepithelial calcium transport across intestinal epithelium-like Caco-2 monolayer"],"prefix":"10.1371","volume":"17","author":[{"given":"Mayuree","family":"Rodrat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kannikar","family":"Wongdee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarinthorn","family":"Teerapornpuntakit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jirawan","family":"Thongbunchoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9080-3303","authenticated-orcid":true,"given":"Duangrudee","family":"Tanramluk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratchaneevan","family":"Aeimlapa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nithipak","family":"Thammayon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natchayaporn","family":"Thonapan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pathnaree","family":"Wattano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2189-6542","authenticated-orcid":true,"given":"Narattaphol","family":"Charoenphandhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"issue":"3","key":"pone.0277096.ref001","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1002\/cphy.c200014","article-title":"Intestinal 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