Regulation of Bile Salt Export Pump mRNA Levels by Dexamethasone and Osmolarity in Cultured Rat Hepatocytes
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Ulrich Warskulat
Abstract
The major canalicular bile salt export pump (Bsep) of mammalian liver is downregulated by endotoxin. This study reports on the effects of dexamethasone and osmolarity on Bsep mRNA expression in cultured rat hepatocytes and its functional relevance in rat liver. Expression of Bsep mRNA in rat hepatocytes 24 and 48 h after isolation was dependent on the presence of dexamethasone (100nm) in the culture medium. Bsep was functionally active at the pseudocanalicular membrane in cells cultured for 4 days in medium containing dexamethasone. Hypoosmolarity (205 mosmol/l) led to an induction of Bsep mRNA levels, whereas expression was decreased by hyperosmolarity (405 mosmol/l). Also the decay of Bsep mRNA following dexamethasone withdrawal was osmosensitive. In rat liver, dexamethasone counteracted the lipopolysaccharide (LPS)-induced down-regulation of Bsep mRNA levels after 12 hours and abolished the LPS-induced inhibition of taurocholate excretion. These results indicate that glucocorticoids are strong inducers of Bsep in liver. Furthermore, Bsep mRNA levels are osmosensitively regulated. The data suggest a long-term control of Bsep mRNA by osmolarity in addition to the short-term effects on canalicular bile acid excretion, which were reported recently.
Copyright (c) 1999 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Secretory Immunoglobulin A: from Mucosal Protection to Vaccine Development
- Cloning of karyopherin-α3 from Drosophila Through Its Interaction with the Nuclear Localization Sequence of Germ Cell-Less Protein
- Regulation of Bile Salt Export Pump mRNA Levels by Dexamethasone and Osmolarity in Cultured Rat Hepatocytes
- High Activity of the Calcineurin A Subunit with a V314 Deletion
- Synthesis, Cytotoxicity and Antitumor Activity of Platinum(II) Complexes of Cyclopentanecarboxylic Acid Hydrazide
- Prion Rods Contain an Inert Polysaccharide Scaffold
- Mass Spectrometric Characterisation of Post-Translational Modification and Genetic Variation in Human Tetranectin
- Complete Amino Acid Sequence Determination of the Major Allergen of Peach (Prunus persica) Pru p1
- Identification of Immunoreactive Tissue Prokallikrein on the Surface Membrane of Human Neutrophils
- An Evaluation of Techniques for the Extraction and Amplification of DNA from Naturally Shed Hairs
- Isolation of Two Novel Alternative Splicing Variants of Allograft Inflammatory Factor-1
- Differential Regulation of Lipid and Protein Kinase Activities of Phosphoinositide 3-Kinase γ in Vitro
- The Anti-Estrogen Hydroxytamoxifen Is a Potent Antagonist in a Novel Yeast System
