| First Author | Hulzebos CV | Year | 2005 |
| Journal | Liver Int | Volume | 25 |
| Issue | 3 | Pages | 604-12 |
| PubMed ID | 15910498 | Mgi Jnum | J:110130 |
| Mgi Id | MGI:3639397 | Doi | 10.1111/j.1478-3231.2005.01036.x |
| Citation | Hulzebos CV, et al. (2005) Bile duct proliferation associated with bile salt-induced hypercholeresis in Mdr2 P-glycoprotein-deficient mice. Liver Int 25(3):604-12 |
| abstractText | BACKGROUND/AIMS: Bile flow consists of bile salt-dependent bile flow (BSDF), generated by canalicular secretion of bile salts, and bile salt-independent flow (BSIF), probably of combined canalicular and ductular origin. Bile salt transport proteins have been identified in cholangiocytes, suggesting a role in control of BSDF and/or in control of bile salt synthesis through cholehepatic shunting. METHODS: We studied effects of bile duct proliferation under non-cholestatic conditions in multidrug resistance-2 P-glycoprotein (Abcb4)-deficient multidrug resistance gene-2 (Mdr2(-/-)) mice. BSDF and BSIF were determined in wild-type and Mdr2(-/-) mice during infusion of step-wise increasing dosages of tauroursodeoxycholate (TUDC). Cholate synthesis rate was determined by 2H4-cholate dilution. Results were related to expression of transport proteins in liver and intestine. RESULTS: During TUDC infusion, BSDF was increased by approximately 50% and BSIF by approximately 100% in Mdr2(-/-) mice compared with controls. Cholate synthesis rate was unaffected in Mdr2(-/-) mice. Hepatic expression of the apical sodium-dependent bile salt transporter (Asbt), its truncated form (tAsbt) and the multidrug resistance-related protein 3 were upregulated in Mdr2(-/-) mice. CONCLUSIONS: Bile duct proliferation in Mdr2(-/-) mice enhances cholehepatic shunting of bile salts, which is associated with a disproportionally high bile flow but does not affect bile salt synthesis. |
