RT Journal Article
SR Electronic
T1 Function of Both Sinusoidal and Canalicular Transporters Controls the Concentration of Organic Anions within Hepatocytes
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1089
OP 1097
DO 10.1124/mol.106.030759
VO 71
IS 4
A1 Corinne Planchamp
A1 Antoine Hadengue
A1 Bruno Stieger
A1 Joëlle Bourquin
A1 Alain Vonlaufen
A1 Jean-Louis Frossard
A1 Rafael Quadri
A1 Christoph D. Becker
A1 Catherine M. Pastor
YR 2007
UL http://molpharm.aspetjournals.org/content/71/4/1089.abstract
AB We hypothesized that the function of both sinusoidal and canalicular transporters importantly controls the concentrations of organic anions within normal hepatocytes. Consequently, we investigated how acute transport regulation of the sinusoidal organic anion transporting polypeptides (Oatps) and the canalicular multidrug resistance associated protein 2 (Mrp2) determines the hepatic concentrations of the organic anion gadolinium benzyloxypropionictetraacetate (BOPTA) in rat livers. Livers were perfused with labeled BOPTA in different experimental settings that modify the function of Oatps and Mrp2 through the protein kinase C (PKC) pathway. Intrahepatic concentrations were continuously measured with a gamma probe placed above rat livers. Labeled BOPTA was also measured in perfusate and bile. We showed that when the function of Oatps and Mrp2 is modified in such a way that BOPTA entry and exit are similarly decreased, concentrations of organic anions within hepatocytes remain unaltered. When exit through Mrp2 is abolished, hepatic concentrations are high if entry through Oatps is only slightly decreased (livers without Mrp2 expression) or low if BOPTA uptake is more importantly decreased (livers perfused with a PKC activator). These results highlight that the function of both sinusoidal and canalicular transporters is important to determine the concentration of organic anions within hepatocytes. The American Society for Pharmacology and Experimental Therapeutics