{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T14:48:48Z","timestamp":1772894928707,"version":"3.50.1"},"reference-count":36,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:p>Human lung epithelial (Calu-3) cells were used to investigate the effects of protease-activated receptor (PAR) stimulation on Cl<jats:sup>\u2212<\/jats:sup>secretion. Quantitative RT-PCR (QRT-PCR) showed that Calu-3 cells express PAR-1, -2, and -3 receptor mRNAs, with PAR-2 mRNA in greatest abundance. Addition of either thrombin or the PAR-2 agonist peptide SLIGRL to the basolateral solution of monolayers mounted in Ussing chambers produced a rapid increase in short-circuit current ( I<jats:sub>sc<\/jats:sub>: thrombin, 21 \u00b1 2 \u03bcA; SLIGRL, 83 \u00b1 22 \u03bcA), which returned to baseline within 5 min after stimulation. Pretreatment of monolayers with the cell-permeant Ca<jats:sup>2+<\/jats:sup>-chelating agent BAPTA-AM (50 \u03bcM) abolished the increase in I<jats:sub>sc<\/jats:sub>produced by SLIGRL. When monolayers were treated with the cyclooxygenase inhibitor indomethacin (10 \u03bcM), nearly complete inhibition of both the thrombin- and SLIGRL-stimulated I<jats:sub>sc<\/jats:sub>was observed. In addition, basolateral treatment with the PGE<jats:sub>2<\/jats:sub>receptor antagonist AH-6809 (25 \u03bcM) significantly inhibited the effects of SLIGRL on I<jats:sub>sc<\/jats:sub>. QRT-PCR revealed that Calu-3 cells express mRNAs for CFTR, the Ca<jats:sup>2+<\/jats:sup>-activated KCNN4 K<jats:sup>+<\/jats:sup>channel, and the KCNQ1 K<jats:sup>+<\/jats:sup>channel subunit, which, in association with KCNE3, is known to be regulated by cAMP. Stimulation with SLIGRL produced an increase in apical Cl<jats:sup>\u2212<\/jats:sup>conductance that was blocked in cells expressing short hairpin RNAs designed to target CFTR. These results support the conclusion that PAR stimulation of Cl<jats:sup>\u2212<\/jats:sup>secretion occurs by an indirect mechanism involving the synthesis and release of prostaglandins. In addition, PAR-stimulated Cl<jats:sup>\u2212<\/jats:sup>secretion requires activation of CFTR and at least two distinct K<jats:sup>+<\/jats:sup>channels located in the basolateral membrane.<\/jats:p>","DOI":"10.1152\/ajpcell.00464.2005","type":"journal-article","created":{"date-parts":[[2006,3,10]],"date-time":"2006-03-10T20:18:13Z","timestamp":1142021893000},"page":"C1189-C1198","source":"Crossref","is-referenced-by-count":43,"title":["Protease-activated receptor regulation of Cl<sup>\u2212<\/sup>secretion in Calu-3 cells requires prostaglandin release and CFTR activation"],"prefix":"10.1152","volume":"290","author":[{"given":"Melissa L.","family":"Palmer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So Yeong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Maniak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Carlson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott C.","family":"Fahrenkrug","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott M.","family":"O'Grady","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Alvarez C, Regan JP, Merianos D, and Bass BL.Protease-activated receptor-2 regulates bicarbonate secretion by pancreatic duct cells in vitro.Surgery136: 669\u2013676, 2004.","DOI":"10.1016\/j.surg.2004.01.018"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Ballard ST, Trout L, Bebok Z, Sorscher EJ, and Crews A.CFTR involvement in chloride, bicarbonate, and liquid secretion by airway submucosal glands.Am J Physiol Lung Cell Mol Physiol277: L694\u2013L699, 1999.","DOI":"10.1152\/ajplung.1999.277.4.L694"},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Bertog M, Letz B, Kong W, Steinhoff M, Higgins MA, Bielfeld-Ackermann A, Fromter E, Bunnett NW, and Korbmacher C.Basolateral proteinase-activated receptor (PAR-2) induces chloride secretion in M-1 mouse renal cortical collecting duct cells.J Physiol521: 3\u201317, 1999.","DOI":"10.1111\/j.1469-7793.1999.00003.x"},{"key":"R4","doi-asserted-by":"crossref","unstructured":"Bleich Mand Warth R.The very small-conductance K+channel KvLQT1 and epithelial function.Pfl\u00fcgers Arch440: 202\u2013206, 2000.","DOI":"10.1007\/s004240000257"},{"key":"R5","doi-asserted-by":"crossref","unstructured":"Buresi MC, Schleihauf E, Vergnolle N, Buret A, Wallace JL, Hollenberg MD, and MacNaughton WK.Protease-activated receptor-1 stimulates Ca2+-dependent Cl\u2212secretion in human intestinal epithelial cells.Am J Physiol Gastrointest Liver Physiol281: G323\u2013G332, 2001.","DOI":"10.1152\/ajpgi.2001.281.2.G323"},{"key":"R6","doi-asserted-by":"crossref","unstructured":"Clayton A, Holland E, Pang L, and Knox A.Interleukin-1\u03b2 differentially regulates \u03b22 adrenoreceptor and prostaglandin E2-mediated cAMP accumulation and chloride efflux from Calu-3 bronchial epithelial cells. 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