Characterization of the Role of ABCG2 as a Bile Acid Transporter in Liver and Placenta
| Autor: | R. Rosales, Doris Cassio, Marta R. Romero, Oscar Briz, Alba G. Blazquez, Javier Vaquero, Jose J.G. Marin, Maria J. Monte, Rocio I.R. Macias |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Organic anion transporter 1 medicine.drug_class Placenta Organic Anion Transporters Sodium-Independent Cell Line Mice chemistry.chemical_compound Cholestasis Pregnancy Internal medicine medicine ATP Binding Cassette Transporter Subfamily G Member 2 Animals Humans Tissue Distribution Pharmacology Membrane Glycoproteins biology Bile acid Cholic acid medicine.disease G protein-coupled bile acid receptor Bile Salt Export Pump Fumitremorgin Neoplasm Proteins Rats Endocrinology medicine.anatomical_structure Liver chemistry embryonic structures biology.protein Molecular Medicine ATP-Binding Cassette Transporters Female sense organs Carrier Proteins |
| Zdroj: | Molecular Pharmacology. 81:273-283 |
| ISSN: | 1521-0111 0026-895X |
| DOI: | 10.1124/mol.111.075143 |
| Popis: | ABCG2 is involved in epithelial transport/barrier functions. Here, we have investigated its ability to transport bile acids in liver and placenta. Cholylglycylamido fluorescein (CGamF) was exported by WIF-B9/R cells, which do not express the bile salt export pump (BSEP). Sensitivity to typical inhibitors suggested that CGamF export was mainly mediated by ABCG2. In Chinese hamster ovary (CHO cells), coexpression of rat Oatp1a1 and human ABCG2 enhanced the uptake and efflux, respectively, of CGamF, cholic acid (CA), glycoCA (GCA), tauroCA, and taurolithocholic acid-3-sulfate. The ability of ABCG2 to export these bile acids was confirmed by microinjecting them together with inulin in Xenopus laevis oocytes expressing this pump. ABCG2-mediated bile acid transport was inhibited by estradiol 17β-d-glucuronide and fumitremorgin C. Placental barrier for bile acids accounted for2-fold increase in fetal cholanemia despite14-fold increased maternal cholanemia induced by obstructive cholestasis in pregnant rats. In rat placenta, the expression of Abcg2, which was much higher than that of Bsep, was not affected by short-term cholestasis. In pregnant rats, fumitremorgin C did not affect uptake/secretion of GCA by the liver but inhibited its fetal-maternal transfer. Compared with wild-type mice, obstructive cholestasis in pregnant Abcg2(-/-) knockout mice induced similar bile acid accumulation in maternal serum but higher accumulation in placenta, fetal serum, and liver. In conclusion, ABCG2 is able to transport bile acids. The importance of this function depends on the relative expression in the same epithelium of other bile acid exporters. Thus, ABCG2 may play a key role in bile acid transport in placenta, as BSEP does in liver. |
| Databáze: | OpenAIRE |
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