title: Expression and function of renal and hepatic organic anion transporters in extrahepatic cholestasis.
abstract: Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct. The absorption, distribution and elimination of drugs are impaired during this pathology. Prolonged cholestasis may alter both liver and kidney function. Lactam antibiotics, diuretics, non-steroidal anti-inflammatory drugs, several antiviral drugs as well as endogenous compounds are classified as organic anions. The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds. It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions. The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis, such as multidrug resistance-associated protein 2, organic anion transporting polypeptide 1, organic anion transporter 3, bilitranslocase, bromosulfophthalein/bilirubin binding protein, organic anion transporter 1 and sodium dependent bile salt transporter. The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.
authors.affiliation: Pharmacology Unit, Department of Physiological Sciences, Faculty of Biochemical and Pharmaceutical Sciences, National University of Rosario, the National Scientific and Technical Research Council, 2000 Rosario, Argentine.
authors.forename: Anabel
authors.initials: A
authors.lastname: Brandoni
authors.forename: María Herminia
authors.initials: MH
authors.lastname: Hazelhoff
authors.forename: Romina Paula
authors.initials: RP
authors.lastname: Bulacio
authors.forename: Adriana Mónica
authors.initials: AM
authors.lastname: Torres
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport; D001651:Cholestasis, Extrahepatic / Q000378:metabolism*; D006801:Humans; D041781:Jaundice, Obstructive / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics
chemical_list: D001647:Bile Acids and Salts; D027361:Organic Anion Transporters; D004364:Pharmaceutical Preparations