Cyclosporin A induced internalization of the bile salt export pump in isolated rat hepatocyte couplets
| Autor: | Jesús A. Fueyo, Irene D Román, Marcelo G. Roma, M. Dolores Fernández-Moreno, Roger Coleman |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty media_common.quotation_subject Biological Transport Active Diaphragm pump Vacuole Biology Toxicology digestive system Tacrolimus Bile Acids and Salts Cholestasis Cyclosporin a Internal medicine medicine Animals Rats Wistar Internalization Cytoskeleton Cells Cultured media_common Dose-Response Relationship Drug Bile Canaliculi Cholic Acids medicine.disease Fluoresceins Bile Salt Export Pump Cell biology Rats Endocrinology medicine.anatomical_structure Hepatocyte Cyclosporine Hepatocytes ATP-Binding Cassette Transporters Immunosuppressive Agents |
| Zdroj: | Toxicological sciences : an official journal of the Society of Toxicology. 71(2) |
| ISSN: | 1096-6080 |
| Popis: | Isolated rat hepatocyte couplets were used to perform the comparative study of two widely used immunosuppressors, cyclosporin A (CsA) and tacrolimus (FK506) on hepatocanalicular function. We assessed canalicular function by counting the percentage of couplets that were able to accumulate the fluorescent cholephile, cholyl-lysyl-fluorescein (CLF), into the canalicular vacuole between the two cells, i.e., canalicular vacuole accumulation (CVA) of CLF. Compared to controls (DMSO-treated cells), CsA, in the approximate range of concentrations used therapeutically, caused inhibition of CVA of CLF, disorganization of the bile salt export pump (Bsep) localization at canalicular level resulting in its relocation into the cell, and disruption of the pericanalicular F-actin cytoskeleton. In contrast, FK506, at both approximately therapeutic and supratherapeutic concentrations, had no deleterious effect upon CVA of CLF, upon the localization of the bile salt transporter at the canalicular membrane, or on the organization of the pericanalicular F-actin cytoskeleton. These results point to transporter and cytoskeletal disorganization as contributors or determinants of CsA-induced cholestasis at canalicular level, whereas FK506 does not appear to produce these cholestasis-determining responses even at supratherapeutic concentrations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|