Bile duct proliferation associated with bile salt-induced hypercholeresis in Mdr2 P-glycoprotein-deficient mice
article
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 ∼ 50% and BSIF by ∼ 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. © Blackwell Munksgaard 2005. Chemicals / CAS: carrier protein, 80700-39-6; chenodeoxycholic acid, 474-25-9; cholic acid, 32500-01-9, 361-09-1, 81-25-4; deoxycholic acid, 83-44-3; lithocholic acid, 434-13-9; multidrug resistance protein 2, 256503-65-8; multidrug resistance protein 3, 231947-64-1; muricholic acid, 39016-49-4; tauroursodeoxycholic acid, 14605-22-2; bile acid binding proteins; Bile Acids and Salts; Carrier Proteins; Cholates; Deuterium, 7782-39-0; Membrane Glycoproteins; Organic Anion Transporters, Sodium-Dependent; P-glycoprotein 2; P-Glycoproteins; Phospholipids; RNA, Messenger; sodium-bile acid cotransporter, 145420-23-1; Symporters
Topics
Bile flowBile formationBile salt synthesisCholangiocyteCholate kineticsCholehepatic shuntbeta actinbile saltbinding proteincarrier proteinchenodeoxycholic acidcholic aciddeoxycholic acidglycoprotein Pileal bile salt binding proteinlithocholic acidmessenger RNAmultidrug resistance protein 2multidrug resistance protein 3muricholic acidtauroursodeoxycholic acidunclassified druganimal experimentanimal modelanimal tissuebile acid synthesiscell proliferationcontrolled studydilutionimmunohistochemistryin vivo studyintestine mucosaintrahepatic bile ductkineticsliver parenchymamalemousenonhumannucleotide sequenceprotein analysisprotein deficiencyprotein expressionupregulationWestern blottingwild typeAnimalsBile Acids and SaltsBile Duct DiseasesBile DuctsCarrier ProteinsCell DivisionCholatesDeuteriumGallbladderIntestinesMembrane GlycoproteinsMiceMice, Mutant StrainsOrganic Anion Transporters, Sodium-DependentP-GlycoproteinsPhospholipidsRNA, MessengerSymporters
TNO Identifier
238519
ISSN
14783223
Source
Liver International, 25(3), pp. 604-612.
Pages
604-612
Files
To receive the publication files, please send an e-mail request to TNO Repository.