{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:34:29Z","timestamp":1790426069398,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2000,11,1]],"date-time":"2000-11-01T00:00:00Z","timestamp":973036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2000,11]]},"abstract":"<jats:p>\n                    This study addresses the mechanisms by which a defect in CFTR impairs pancreatic duct bicarbonate secretion in cystic fibrosis. We used control (PANC\u20101) and CFTR\u2010deficient (CFPAC\u20101; \u0394F508 mutation) cell lines and measured HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    extrusion by the rate of recovery of intracellular pH after an alkaline load and recorded whole cell membrane currents using patch clamp techniques.\n                    <jats:italic>1)<\/jats:italic>\n                    In PANC\u20101 cells, cAMP causes parallel activation of Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    channels and of HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    extrusion by DIDS\u2010sensitive and Na\n                    <jats:sup>+<\/jats:sup>\n                    \u2010independent Cl\n                    <jats:sup>\u2010<\/jats:sup>\n                    \/HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    exchange, both effects being inhibited by Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    channel blockers NPPB and glibenclamide.\n                    <jats:italic>2)<\/jats:italic>\n                    In CFPAC\u20101 cells, cAMP fails to stimulate Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/ HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    exchange and Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    channels, except after promoting surface expression of \u0394F508\u2010CFTR by glycerol treatment. Instead, raising intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentration to 1 \u03bcmol\/l or stimulating purinergic receptors with ATP (10 and 100 \u03bcmol\/l) leads to parallel activation of Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    channels and HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    extrusion.\n                    <jats:italic>3)<\/jats:italic>\n                    K\n                    <jats:sup>+<\/jats:sup>\n                    channel function is required for coupling cAMP\u2010 and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    channel activation to effective stimulation of Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    exchange in control and CF cells, respectively. It is concluded that stimulation of pancreatic duct bicarbonate secretion via Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/ HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    exchange is directly correlated to activation of apical membrane Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    channels. Reduced bicarbonate secretion in cystic fibrosis results from defective cAMP\u2010activated Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    channels. This defect is partially compensated for by an increased sensitivity of CF cells to purinergic stimulation and by alternative activation of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    channels, mechanisms of interest with respect to possible treatment of cystic fibrosis and of related chronic pancreatic diseases.\u2014Zsembery, A., Strazzabosco, M., Graf, J. Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010activated Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    channels can substitute for CFTR in stimulation of pancreatic duct bicarbonate secretion.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    14, 2345\u20132356 (2000)\n                  <\/jats:p>","DOI":"10.1096\/fj.99-0509com","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:03:24Z","timestamp":1027710204000},"page":"2345-2356","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Ca\n                    <sup>2+<\/sup>\n                    \u2010activated Cl\n                    <sup>\u2212<\/sup>\n                    channels can substitute for CFTR in stimulation of pancreatic duct bicarbonate secretion"],"prefix":"10.1096","volume":"14","author":[{"given":"\u00c1kos","family":"ZSEMBERY","sequence":"first","affiliation":[{"name":"Department of General and Experimental Pathology University of Vienna Vienna Austria"},{"name":"Istituto di Medicina Interna Universit\u00e0 ed Azienda Ospedaliera di Padova Padua Italy"},{"name":"Department of Pathophysiology Semmelweis University Faculty of Medicine Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Strazzabosco","sequence":"additional","affiliation":[{"name":"Istituto di Medicina Interna Universit\u00e0 ed Azienda Ospedaliera di Padova Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00dcrg","family":"Graf","sequence":"additional","affiliation":[{"name":"Department of General and Experimental Pathology University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2000,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(92)90866-W"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1992.263.2.C267"},{"key":"e_1_2_6_4_1","first-page":"2","article-title":"Pathophysiology of the exocrine pancreas in cystic fibrosis","volume":"82","author":"Durie P. 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