{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:34:02Z","timestamp":1773308042081,"version":"3.50.1"},"reference-count":48,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2001,8,1]]},"abstract":"<jats:p>Cholangiocytes absorb and secrete fluid, modifying primary canalicular bile. In several Cl<jats:sup>\u2212<\/jats:sup>-secreting epithelia, Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransport is a basolateral Cl<jats:sup>\u2212<\/jats:sup>uptake pathway facilitating apical Cl<jats:sup>\u2212<\/jats:sup>secretion. To determine if cholangiocytes possess similar mechanisms independent of CO<jats:sub>2<\/jats:sub>\/HCO[Formula: see text], we assessed Cl<jats:sup>\u2212<\/jats:sup>-dependent secretion in rat liver isolated polarized bile duct units (IBDUs) by using videomicroscopy. Without CO<jats:sub>2<\/jats:sub>\/HCO[Formula: see text], forskolin (FSK) stimulated secretion entirely dependent on Na<jats:sup>+<\/jats:sup>and Cl<jats:sup>\u2212<\/jats:sup>and inhibited by Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>inhibitor bumetanide. Carbonic anhydrase inhibitor ethoxyzolamide had no effect on FSK-stimulated secretion, indicating negligible endogenous CO<jats:sub>2<\/jats:sub>\/HCO[Formula: see text] transport. In contrast, FSK-stimulated secretion was inhibited \u223c85% by K<jats:sup>+<\/jats:sup>channel inhibitor Ba<jats:sup>2+<\/jats:sup>and blocked completely by bumetanide plus Ba<jats:sup>2+<\/jats:sup>. IBDU Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransport activity was assessed by recording intracellular pH during NH<jats:sub>4<\/jats:sub>Cl exposure. Bumetanide inhibited initial acidification rates due to NH[Formula: see text] entry in the presence and absence of CO<jats:sub>2<\/jats:sub>\/HCO[Formula: see text]. In contrast, when stimulated by FSK, a 35% increase in Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransport activity occurred without CO<jats:sub>2<\/jats:sub>\/HCO[Formula: see text]. These data suggest a cellular model of HCO[Formula: see text]-independent secretion in which Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransport maintains high intracellular Cl<jats:sup>\u2212<\/jats:sup>concentration. Intracellular cAMP concentration increases activate basolateral K<jats:sup>+<\/jats:sup>conductance, raises apical Cl<jats:sup>\u2212<\/jats:sup>permeability, and causes transcellular Cl<jats:sup>\u2212<\/jats:sup>movement into the lumen. Polarized IBDU cholangiocytes are capable of vectorial Cl<jats:sup>\u2212<\/jats:sup>-dependent fluid secretion independent of HCO[Formula: see text]. Bumetanide-sensitive Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransport, Cl<jats:sup>\u2212<\/jats:sup>\/HCO[Formula: see text] exchange, and Ba<jats:sup>2+<\/jats:sup>-sensitive K<jats:sup>+<\/jats:sup>channels are important components of stimulated fluid secretion in intrahepatic bile duct epithelium.<\/jats:p>","DOI":"10.1152\/ajpgi.2001.281.2.g438","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T15:33:10Z","timestamp":1514129590000},"page":"G438-G446","source":"Crossref","is-referenced-by-count":19,"title":["Cl<sup>\u2212<\/sup>-dependent secretory mechanisms in isolated rat bile duct epithelial units"],"prefix":"10.1152","volume":"281","author":[{"given":"Satish K.","family":"Singh","sequence":"first","affiliation":[{"name":"Liver Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8019; and"},{"name":"Evans Biomedical Research Center, Department 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