Different pathways of canalicular secretion of sulfated and non-sulfated fluorescent bile acids: a study in isolated hepatocyte couplets and TR- rats
| Autor: | Elwyn Elias, Folkert Kuipers, Piotr Milkiewicz, Michael Müller, Rick Havinga, Roger Coleman, Peter L.M. Jansen, Charles O. Mills, Marcelo G. Roma |
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| Přispěvatelé: | Other departments, Center for Liver, Digestive and Metabolic Diseases (CLDM) |
| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
Male
BILIARY-EXCRETION MUTANT RATS medicine.drug_class LYSYL-FLUORESCEIN Anion Transport Proteins PROTEIN Contrast Media digestive system Fluorescence Rats Mutant Strains Bile canaliculus Bile Acids and Salts chemistry.chemical_compound In vivo lysyl fluorescein conjugated bile acid analogues HEPATOBILIARY ORGANIC-ANIONS medicine Animals TRANSPORT-SYSTEMS Fluorescein Rats Wistar TR- rats Hepatology Bile acid biology DERIVATIVES Sulfates Bile Canaliculi Cholic Acids Fluoresceins Bile Salt Export Pump In vitro eye diseases hepatocyte couplets Rats medicine.anatomical_structure chemistry Biochemistry Liver canalicular secretion Hepatocyte mrp2 biology.protein MEMBRANE Carrier Proteins Organic anion |
| Zdroj: | Journal of hepatology, 31(4), 678-684. Elsevier Journal of Hepatology, 31(4), 678-684. ELSEVIER SCIENCE BV |
| ISSN: | 0168-8278 |
| DOI: | 10.1016/s0168-8278(99)80348-1 |
| Popis: | Background/Aims: Fluorescent bile acids have proved useful for characterizing bile salt transport mechanisms. The aim of this study was to further validate the use of lysyl-fluorescein conjugated bile acid analogues as surrogate bile acids. Methods: We analyzed biliary excretion kinetics of cholyl lysyl fluorescein (CLF), lithocholyl lysyl fluorescein (LLF) and sulfo-lithocholyl lysyl fluorescein (sLLF), both in the isolated rat hepatocyte couplet model and in TR − rats with a selective canalicular transport defect of non-bile acid organic anions. Results: CLF and LLF, which like their natural nonsulfated bile acid congeners are expected to behandled by the canalicular bile salt export pump, were transferred into the bile canaliculus much faster than sLLF, a putative substrate for the canalicular multispecific organic anion transporter in both the in vivo and the in vitro models employed. The contention that different transport systems are involved in sulfated and non-sulfated lysyl fluorescein conjugated bile acids biliary excretion was supported further by studies using TR − rats, in which the cumulative biliary excretion of sLLF was reduced to 6% as compared with that of normal Wistar rats, in good agreement with values for its naturally-occurring radiolabeled parent compound sulfoglycolithocholate. In contrast, CLF and LLF were reduced to 66% and 52%, similar values to these for their congeners, [ 14 C] glycocholate and [ 14 C] lithocholate. Conclusion: The close similarity in behavior of lysyl fluorescein conjugated bile acids to that of their naturally-occurring parent compounds in these different models gives support for both sulfated and nonsulfated lysyl fluorescein conjugated bile acids as substitute molecules for studies of bile acid transport. |
| Databáze: | OpenAIRE |
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