Function of both sinusoidal and canalicular transporters controls the concentration of organic anions within hepatocytes

Planchamp Messeiller, Corinne; Hadengue, Antoine; Stieger, Bruno; Bourquin, Joelle; Vonlaufen, Alain; Frossard, Jean-Louis; Quadri Defilippis, Rafael; Becker, Christoph; Pastor, Catherine

doi:10.1124/mol.106.030759

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Title		Function of both sinusoidal and canalicular transporters controls the concentration of organic anions within hepatocytes
Authors		Planchamp Messeiller, Corinne Hadengue, Antoine Stieger, Bruno Bourquin, Joelle Vonlaufen, Alain Frossard, Jean-Louis Quadri Defilippis, Rafael Becker, Christoph Pastor, Catherine show all authors [1 - 9]
Published in		Molecular pharmacology. 2007, vol. 71, no. 4, p. 1089-97
Abstract		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 (Mrp(2)) 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 Mrp(2) 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 Mrp(2) 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 Mrp(2) is abolished, hepatic concentrations are high if entry through Oatps is only slightly decreased (livers without Mrp(2) 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.
Keywords		ATP-Binding Cassette Transporters/metabolism — Animals — Anions/pharmacokinetics — Biological Transport — Hepatocytes/metabolism — Liver/cytology/metabolism — Organic Anion Transporters/metabolism — Organic Chemicals/pharmacokinetics — Protein Kinase C/metabolism — Rats — Rats, Sprague-Dawley
Identifiers		DOI: 10.1124/mol.106.030759 PMID: 17234897
Full text		Article (Published version) (495 Kb) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine clinique / Département de radiologie et informatique médicale
Research group		Pharmacologie et imagerie du foie (664)
Citation (ISO format)		PLANCHAMP MESSEILLER, Corinne et al. Function of both sinusoidal and canalicular transporters controls the concentration of organic anions within hepatocytes. In: Molecular pharmacology, 2007, vol. 71, n° 4, p. 1089-97. doi: 10.1124/mol.106.030759 https://archive-ouverte.unige.ch/unige:43353