Cholangiocyte anion exchange and biliary bicarbonate excretion.
Primary canalicular bile undergoes a process of fluidization and alkalinization along the biliary tract that is influenced by several factors including hormones, innervation/neuropeptides, and biliary constituents. The excretion of bicarbonate at both the canaliculi and the bile ducts is an important contributor to the generation of the so-called bile-salt independent flow. Bicarbonate is secreted from hepatocytes and cholangiocytes through parallel mechanisms which involve chloride efflux through activation of Cl- channels, and further bicarbonate secretion via AE2/SLC4A2-mediated Cl-/HCO3- exchange. Glucagon and secretin are two relevant hormones which seem to act very similarly in their target cells (hepatocytes for the former and cholangiocytes for the latter). These hormones interact with their specific G protein-coupled receptors, causing increases in intracellular levels of cAMP and activation of cAMP-dependent Cl- and HCO3- secretory mechanisms. Both hepatocytes and cholangiocytes appear to have cAMP-responsive intracellular vesicles in which AE2/SLC4A2 colocalizes with cell specific Cl- channels (CFTR in cholangiocytes and not yet determined in hepatocytes) and aquaporins (AQP8 in hepatocytes and AQP1 in cholangiocytes). cAMP-induced coordinated trafficking of these vesicles to either canalicular or cholangiocyte lumenal membranes and further exocytosis results in increased osmotic forces and passive movement of water with net bicarbonate-rich hydrocholeresis.
Banales
Jesús-M
JM
Laboratory of Molecular Genetics, Division of Gene Therapy and Hepatology, University of Navarra School of Medicine, Clinica Universitaria and CIMA, Avda. Pio XII 55, E-31008 Pamplona, Spain.
Prieto
Jesus
J
Medina
Juan-F
JF
D000818:Animals; D017920:Antiporters / Q000032:analysis / Q000502:physiology*; D020346:Aquaporins / Q000032:analysis / Q000502:physiology; D001639:Bicarbonates / Q000378:metabolism*; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000032:analysis / Q000502:physiology; D001652:Bile Ducts / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D018118:Chloride Channels / Q000032:analysis / Q000502:physiology; D002712:Chlorides / Q000032:analysis / Q000378:metabolism; D000242:Cyclic AMP / Q000032:analysis / Q000502:physiology; D005934:Glucagon / Q000032:analysis / Q000502:physiology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000294:innervation / Q000502:physiology; D009995:Osmosis; D011983:Receptors, Purinergic / Q000032:analysis / Q000502:physiology; D012633:Secretin / Q000032:analysis / Q000502:physiology
D017920:Antiporters; D020346:Aquaporins; D001639:Bicarbonates; D001647:Bile Acids and Salts; D018118:Chloride Channels; D002712:Chlorides; D011983:Receptors, Purinergic; D012633:Secretin; D005934:Glucagon; D000242:Cyclic AMP