Effects of bile salt flux variations on the expression of hepatic bile salt transporters in vivo in mice.
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Wolters H, Elzinga BM, Baller JF, Boverhof R, Schwarz M, Stieger B, Verkade HJ, Kuipers F
Effects of bile salt flux variations on the expression of hepatic bile salt transporters in vivo in mice.
J Hepatol. 2002 Nov;37(5):556-63.
- PubMed ID
- 12399219 [ View in PubMed]
- Abstract
BACKGROUND/AIMS: Expression of hepatic bile salt transporters is partly regulated by bile salts via activation of nuclear farnesoid X-activated receptor (Fxr). We investigated the physiological relevance of this regulation by evaluating transporter expression in mice experiencing different transhepatic bile salt fluxes. METHODS: Bile salt flux was manipulated by dietary supplementation with taurocholate (0.5% w/w) or cholestyramine (2% w/w) or by disruption of the cholesterol 7alpha-hydroxylase-gene (Cyp7A(-/-) mice) leading to reduced bile salt pool size. Expression of hepatic transporters was assessed (polymerase chain reaction (PCR), immunoblotting, and immunohistochemistry). RESULTS: Biliary bile salt secretion was increased (+350%) or decreased (-50%) after taurocholate or cholestyramine feeding, respectively, but plasma bile salt concentrations and hepatic Fxr expression were not affected. The bile salt uptake system Na(+)-taurocholate co-transporting polypeptide (Ntcp) and organic anion transporting polypeptide-1 (Oatp1) were down-regulated by taurocholate and not affected by cholestyramine feeding. Cyp7A(-/-) mice did not show altered Ntcp or Oatp1 expression. Canalicular bile salt export pump (Bsep) was up-regulated by 65% in taurocholate-fed mice, and slightly down-regulated in Cyp7A(-/-) mice. CONCLUSIONS: Large variations in hepatic bile salt flux have minor effects on expression of murine Ntcp and Bsep in vivo, suggesting that these transporters are abundantly expressed and able to accommodate a wide range of 'physiological' bile salt fluxes.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Taurocholic acid Bile salt export pump Protein Humans UnknownSubstrateInducerDetails Taurocholic acid Ileal sodium/bile acid cotransporter Protein Humans UnknownSubstrateInducerDetails Taurocholic acid Solute carrier organic anion transporter family member 1A2 Protein Humans UnknownSubstrateInhibitorInducerDetails