Document Detail


The biliary HCO(3)(-) umbrella: a unifying hypothesis on pathogenetic and therapeutic aspects of fibrosing cholangiopathies.
MedLine Citation:
PMID:  20721884     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This review focuses on the hypothesis that biliary HCO(3)(-) secretion in humans serves to maintain an alkaline pH near the apical surface of hepatocytes and cholangiocytes to prevent the uncontrolled membrane permeation of protonated glycine-conjugated bile acids. Functional impairment of this biliary HCO(3)(-) umbrella or its regulation may lead to enhanced vulnerability of cholangiocytes and periportal hepatocytes toward the attack of apolar hydrophobic bile acids. An intact interplay of hepatocellular and cholangiocellular adenosine triphosphate (ATP) secretion, ATP/P2Y- and bile salt/TGR5-mediated Cl(-)/ HCO(3)(-) exchange and HCO(3)(-) secretion, and alkaline phosphatase-mediated ATP breakdown may guarantee a stable biliary HCO(3)(-) umbrella under physiological conditions. Genetic and acquired functional defects leading to destabilization of the biliary HCO(3)(-) umbrella may contribute to development and progression of various forms of fibrosing/sclerosing cholangitis.
Authors:
Ulrich Beuers; Simon Hohenester; Lucas J Maillette de Buy Wenniger; Andreas E Kremer; Peter L M Jansen; Ronald P J Oude Elferink
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  52     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-29     Completed Date:  2010-10-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1489-96     Citation Subset:  IM    
Affiliation:
Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. u.h.beuers@amc.uva.nl
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism,  secretion
Animals
Bicarbonates / metabolism*
Bile Acids and Salts / metabolism,  toxicity
Bile Ducts / secretion*
Chloride-Bicarbonate Antiporters / physiology*
Cholangitis, Sclerosing / drug therapy*,  etiology*,  physiopathology
Humans
Hydrogen-Ion Concentration
Micelles
Phospholipids / metabolism
Receptors, Purinergic P2 / physiology*
Chemical
Reg. No./Substance:
0/Bicarbonates; 0/Bile Acids and Salts; 0/Chloride-Bicarbonate Antiporters; 0/Micelles; 0/Phospholipids; 0/Receptors, Purinergic P2; 56-65-5/Adenosine Triphosphate

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