Function of both sinusoidal and canalicular transporters controls the concentration of organic anions within hepatocytes
| العنوان: | Function of both sinusoidal and canalicular transporters controls the concentration of organic anions within hepatocytes |
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| المؤلفون: | Alain Vonlaufen, Joëlle Bourquin, Christoph D. Becker, Bruno Stieger, Rafael Quadri, Antoine Hadengue, Corinne Planchamp, Jean-Louis Frossard, Catherine M. Pastor |
| المصدر: | Molecular pharmacology Molecular Pharmacology, Vol. 71, No 4 (2007) pp. 1089-97 |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Anions, Organic Anion Transporters, Protein Kinase C/metabolism, ddc:616.0757, Organic Chemicals/pharmacokinetics, Organic Anion Transporters/metabolism, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Animals, Liver/cytology/metabolism, ATP-Binding Cassette Transporters/metabolism, Organic Chemicals, Protein kinase C, Protein Kinase C, 030304 developmental biology, Pharmacology, ddc:616, 0303 health sciences, ddc:615, biology, Activator (genetics), Chemistry, Multidrug resistance-associated protein 2, Hepatocytes/metabolism, Transporter, Biological Transport, Rats, Biochemistry, Liver, Anions/pharmacokinetics, 030220 oncology & carcinogenesis, biology.protein, Hepatocytes, Molecular Medicine, ATP-Binding Cassette Transporters, Function (biology), Organic anion |
| الوصف: | 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. |
| تدمد: | 0026-895X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8ad487d67be4c44728fee288287a5a0Test https://pubmed.ncbi.nlm.nih.gov/17234897Test |
| حقوق: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....e8ad487d67be4c44728fee288287a5a0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 0026895X |
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