• 1
    Banales JM, Prieto J, Medina JF. Cholangiocyte anion exchange and biliary bicarbonate excretion. World J Gastroenterol 2006; 12: 34963511.
  • 2
    Strazzabosco M, Mennone A, Boyer JL. Intracellular pH regulation in isolated rat bile duct epithelial cells. J Clin Invest 1991; 87: 15031512.
  • 3
    Strazzabosco M, Joplin R, Zsembery A, Wallace L, Spirlí C, Fabris L, et al. Na+-dependent and independent Cl/HCOmath image exchange mediate cellular HCO3 transport in cultured human intrahepatic bile duct cells. HEPATOLOGY 1997; 25: 976985.
  • 4
    Arenas F, Hervias I, Uriz M, Joplin R, Prieto J, Medina JF. Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells. J Clin Invest 2008; 118: 695709.
  • 5
    Banales JM, Arenas F, Rodriguez-Ortigosa CM, Saez E, Uriarte I, Doctor RB, et al. Bicarbonate-rich choleresis induced by secretin in normal rat is taurocholate-dependent and involves AE2 anion exchanger. HEPATOLOGY 2006; 43: 266275.
  • 6
    Alper SL. Molecular physiology and genetics of Na+-independent SLC4 anion exchangers. J Exp Biol 2009; 212: 16721683.
  • 7
    Tietz PS, Marinelli RA, Chen XM, Huang B, Cohn J, Kole J, et al. Agonist-induced coordinated trafficking of functionally related transport proteins for water and ions in cholangiocytes. J Biol Chem 2003; 278: 2041320419.
  • 8
    Lenzen R, Alpini G, Tavoloni N. Secretin stimulates bile ductular secretory activity through the cAMP system. Am J Physiol 1992; 263: G527G532.
  • 9
    Roberts SK, Kuntz SM, Gores GJ, LaRusso NF. Regulation of bicarbonate-dependent ductular bile secretion assessed by lumenal micropuncture of isolated rodent intrahepatic bile ducts. Proc Natl Acad Sci USA 1993; 90: 90809084.
  • 10
    Alvaro D, Mennone A, Boyer JL. Role of kinases and phosphatases in the regulation of fluid secretion and Cl/HCOmath image exchange in cholangiocytes. Am J Physiol 1997; 273: G303G313.
  • 11
    McGill JM, Basavappa S, Gettys TW, Fitz JG. Secretin activates Cl channels in bile duct epithelial cells through a cAMP-dependent mechanism. Am J Physiol 1994; 266: G731G736.
  • 12
    Marinelli RA, Gradilone SA, Carreras FI, Calamita G, Lehmann GL. Liver aquaporins: significance in canalicular and ductal bile formation. Ann Hepatol 2004; 3: 130136.
  • 13
    Minagawa N, Nagata J, Shibao K, Masyuk AI, Gomes DA, Rodrigues MA, et al. Cyclic AMP regulates bicarbonate secretion in cholangiocytes through release of ATP into bile. Gastroenterology 2007; 133: 15921602.
  • 14
    Nathanson MH, Burgstahler AD, Mennone A, Boyer JL. Characterization of cytosolic Ca2+ signaling in rat bile duct epithelia. Am J Physiol 1996; 271: G86G96.
  • 15
    Alvaro D, Alpini G, Jezequel AM, Bassotti C, Francia C, Fraioli F, et al. Role and mechanisms of action of acetylcholine in the regulation of rat cholangiocyte secretory functions. J Clin Invest 1997; 100: 13491362.
  • 16
    Prieto J, Qian C, Garcia N, Diez J, Medina JF. Abnormal expression of anion exchanger genes in primary biliary cirrhosis. Gastroenterology 1993; 105: 572578.
  • 17
    Medina JF, Martinez A, Vazquez JJ, Prieto J. Decreased anion exchanger 2 immunoreactivity in the liver of patients with primary biliary cirrhosis. HEPATOLOGY 1997; 25: 1217.
  • 18
    Melero S, Spirlí C, Zsembery A, Medina JF, Joplin RE, Duner E, et al. Defective regulation of cholangiocyte Cl/HCO3 and Na+/H+ exchanger activities in primary biliary cirrhosis. HEPATOLOGY 2002; 35: 15131521.
  • 19
    Medina JF, Recalde S, Prieto J, Lecanda J, Saez E, Funk CD, et al. Anion exchanger 2 is essential for spermiogenesis in mice. Proc Natl Acad Sci USA 2003; 100: 1584715852.
  • 20
    Salas JT, Banales JM, Sarvide S, Recalde S, Ferrer A, Uriarte I, et al. Ae2a,b-deficient mice develop antimitochondrial antibodies and other features resembling primary biliary cirrhosis. Gastroenterology 2008; 134: 14821493.
  • 21
    Mardones P, Medina JF, Elferink RP. Activation of cyclic AMP Signaling in Ae2-deficient mouse fibroblasts. J Biol Chem 2008; 283: 1214612153.
  • 22
    Spirlí C, Granato A, Zsembery K, Anglani F, Okolicsanyi L, LaRusso NF, et al. Functional polarity of Na+/H+ and Cl/HCOmath image exchangers in a rat cholangiocyte cell line. Am J Physiol 1998; 275: G1236G1245.
  • 23
    Zsembery A, Spirli C, Granato A, LaRusso NF, Okolicsanyi L, Crepaldi G, et al. Purinergic regulation of acid/base transport in human and rat biliary epithelial cell lines. Hepatology 1998; 28: 914920.
  • 24
    Salter KD, Roman RM, LaRusso NR, Fitz JG, Doctor RB. Modified culture conditions enhance expression of differentiated phenotypic properties of normal rat cholangiocytes. Lab Invest 2000; 80: 17751778.
  • 25
    Romero MF, Fulton CM, Boron WF. The SLC4 family of HCO3 transporters. Pflugers Arch 2004; 447: 495509.
  • 26
    Pushkin A, Kurtz I. SLC4 base (HCOmath image, CO32−) transporters: classification, function, structure, genetic diseases, and knockout models. Am J Physiol Renal Physiol 2006; 290: F580F599.
  • 27
    Pushkin A, Abuladze N, Lee I, Newman D, Hwang J, Kurtz I. Cloning, tissue distribution, genomic organization, and functional characterization of NBC3, a new member of the sodium bicarbonate cotransporter family. J Biol Chem 1999; 274: 1656916575.
  • 28
    Gross E, Hawkins K, Pushkin A, Sassani P, Dukkipati R, Abuladze N, et al. Phosphorylation of Ser982 in the sodium bicarbonate cotransporter kNBC1 shifts the HCOmath image:Na+ stoichiometry from 3:1 to 2:1 in murine proximal tubule cells. J Physiol 2001; 537: 659665.
  • 29
    Choi I, Aalkjaer C, Boulpaep EL, Boron WF. An electroneutral sodium/bicarbonate cotransporter NBCn1 and associated sodium channel. Nature 2000; 405: 571575.
  • 30
    Roman RM, Feranchak AP, Salter KD, Wang Y, Fitz JG. Endogenous ATP release regulates Cl secretion in cultured human and rat biliary epithelial cells. Am J Physiol 1999; 276: G1391G1400.
  • 31
    Salter KD, Fitz JG, Roman RM. Domain-specific purinergic signaling in polarized rat cholangiocytes. Am J Physiol Gastrointest Liver Physiol 2000; 278: G492G500.
  • 32
    Prieto J, García N, Martí-Climent JM, Peñuelas I, Richter JA, Medina JF. Assessment of biliary bicarbonate secretion in humans by positron emission tomography. Gastroenterology 1999; 117: 167172.
  • 33
    Alvaro D, Cho WK, Mennone A, Boyer JL. Effect of secretion on intracellular pH regulation in isolated rat bile duct epithelial cells. J Clin Invest 1993; 92: 13141325.
  • 34
    Mennone A, Alvaro D, Cho W, Boyer JL. Isolation of small polarized bile duct units. Proc Natl Acad Sci USA 1995; 92: 65276531.
  • 35
    Dutta AK, Woo K, Doctor RB, Fitz JG, Feranchak AP. Extracellular nucleotides stimulate Cl currents in biliary epithelia through receptor-mediated IP3 and Ca2+ release. Am J Physiol Gastrointest Liver Physiol 2008; 295: G1004G1015.
  • 36
    Ko SB, Shcheynikov N, Choi JY, Luo X, Ishibashi K, Thomas PJ, et al. A molecular mechanism for aberrant CFTR-dependent HCO3 transport in cystic fibrosis. EMBO J 2002; 21: 56625672.
  • 37
    Zsembery A, Jessner W, Sitter G, Spirlí C, Strazzabosco M, Graf J. Correction of CFTR malfunction and stimulation of Ca2+-activated Cl channels restore HCOmath image secretion in cystic fibrosis bile ductular cells. HEPATOLOGY 2002; 35: 95104.
  • 38
    Spirlí C, Fiorotto R, Song L, Santos-Sacchi J, Okolicsanyi L, Masier S, et al. Glibenclamide stimulates fluid secretion in rodent cholangiocytes through a cystic fibrosis transmembrane conductance regulator-independent mechanism. Gastroenterology 2005; 129: 220233.