Regulation of protein secretion into bile: studies in mice with a disrupted mdr2 p-glycoprotein gene
| Autor: | Jaap J.M. Smit, Michel J.A. van Wijland, Wilma M. Frederiks, Ronald P.J. Oude Elferink, Albert K. Groen, Alfred H. Schinkel |
|---|---|
| Přispěvatelé: | Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 1995 |
| Předmět: |
Taurocholic Acid
Cholagogues and Choleretics medicine.medical_specialty Phosphoric monoester hydrolases Phospholipid Enzyme-Linked Immunosorbent Assay Mice Transgenic CD13 Antigens Biology Aminopeptidase Exocytosis Taurochenodeoxycholic Acid Mice chemistry.chemical_compound Internal medicine medicine Animals Bile Secretion ATP Binding Cassette Transporter Subfamily B Member 1 Phospholipids chemistry.chemical_classification Hepatology Gastroenterology Proteins Alkaline Phosphatase Lipid Metabolism Enzyme Endocrinology Secretory protein Genes chemistry Mutation Alkaline phosphatase |
| Zdroj: | Gastroenterology, 109(6), 1997-2006. W.B. Saunders Ltd |
| ISSN: | 0016-5085 |
| Popis: | Background & Aims: Protein is secreted into bile via several independent pathways. The aim of this study was to investigate whether these pathways are influenced by secretion of biliary lipid. Methods: Protein secretion and biliary lipid output were studied in wildtype mice (+/+), heterozygotes (+/−), and homozygotes (−/−) for mdr2 gene disruption. Biliary lipid and protein output were varied by infusion with taurocholate (TC) and tauroursodeoxycholate (TUDC). Results: Exocytosis and transcytosis were unaltered in (−/−) mice. Infusion with TC strongly induced secretion of alkaline phosphatase in (−/−) mice but had little effect in (+/−) and (+/+) mice. Infusion with TUDC had little effect on alkaline phosphatase output. In contrast, both TUDC and TC strongly stimulated secretion of aminopeptidase N and lysosomal enzymes in (+/+) mice but had no effect in (−/−) animals. Aminopeptidase N secretion correlated with phospholipid output, but only at high flux. At low flux, aminopeptidase N was secreted independently from both phospholipid and bile salts. Conclusions: The canalicular membrane enzymes alkaline phosphatase and aminopeptidase N are secreted via separate pathways. Part of alkaline phosphatase output is controlled by bile salt hydrophobicity, whereas at high lipid flux, aminopeptidase N secretion seems to be coupled to phospholipid output. Lysosomal enzymes follow the latter pathway. |
| Databáze: | OpenAIRE |
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