The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Abcb4  -  ATP-binding cassette, subfamily B...

Rattus norvegicus

Synonyms: ATP-binding cassette sub-family B member 4, Mdr2, Multidrug resistance protein 2, Multidrug resistance protein 3, P-glycoprotein 2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Abcb4


High impact information on Abcb4

  • RESULTS: In diabetic rats, hepatic gene and protein expression of the multidrug resistance P-glycoprotein type 2 (Mdr2) were increased by 105% and 530%, respectively, associated with increased biliary phospholipid output (+520%) and phospholipid/bile salt ratio (+77%) [3].
  • Mdr2((-/-)) mice do not secrete phospholipids and cholesterol into bile, and bile salt secretion is not impaired [4].
  • BACKGROUND & AIMS: Endotoxin lipopolysaccharide (LPS) induces cholestasis and down-regulates the multidrug resistance protein 2 (MRP2) [5].
  • Dexamethasone counteracted the LPS effects on MRP2 mRNA levels, subcellular distribution, and BSP excretion [5].
  • CONCLUSIONS: LPS induces cholestasis due to an early retrieval of MRP2 from the canalicular membrane, whereas down-regulation of MRP2 mRNA is a later event [5].

Chemical compound and disease context of Abcb4


Biological context of Abcb4

  • Cholestasis induces down-regulation of multidrug resistance protein 2 (Mrp2, symbol Abcc2), which is localized to the canalicular membrane [8].
  • In summary, the increase in Mrp2 protein after microsomal enzyme induction is responsible for increased biliary DBSP excretion [9].
  • Transient transfection assays with reporter vectors containing unidirectionally deleted 5'-flanking regions using H4IIE cells indicate that two different sequences of 17 and 37 bases comprising a Y-Box and a GC-Box are required for mrp2 gene basal expression [2].
  • To further examine the substrate specificity of Mrp2, we examined the effects of bile acid sulfates on the biliary excretion of phenolphthalein sulfate in rats [10].
  • (2) Bsep- and Mrp2-specific vesicles participate in the short-term osmoregulation of canalicular secretion, however, a cause-effect relationship between bile salt excretion and transporter localization remains to be established [11].

Anatomical context of Abcb4

  • Our results indicate that phalloidin induces marked alterations of the hepatocyte canalicular architecture and a loss of Mrp2 together with other proteins from the canalicular membrane [1].
  • Confocal immunofluorescent microscopy showed asynchronous appearance of Bsep and Mrp2 proteins during development but their colocalization in the bile canaliculi once each one is expressed [12].
  • Expression and immunolocalization of multidrug resistance protein 2 in rabbit small intestine [13].
  • The present study demonstrates exclusive localization of Mrp2 to the brush-border (apical) membrane of villi, decreasing in intensity from the villus tip to the crypts [13].
  • In immunoblot analysis of crude membranes of various rabbit tissues, Mrp2 was only found in small intestine, kidney and liver [13].

Associations of Abcb4 with chemical compounds


Other interactions of Abcb4

  • Furthermore, in vivo administration of AAF, which maximally induces PGP does not induce MRP2 [16].

Analytical, diagnostic and therapeutic context of Abcb4


  1. Changes in the localization of the rat canalicular conjugate export pump Mrp2 in phalloidin-induced cholestasis. Rost, D., Kartenbeck, J., Keppler, D. Hepatology (1999) [Pubmed]
  2. Sequence analysis and functional characterization of the 5'-flanking region of the rat multidrug resistance protein 2 (mrp2) gene. Kauffmann, H.M., Schrenk, D. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  3. Differential effects of streptozotocin-induced diabetes on expression of hepatic ABC-transporters in rats. van Waarde, W.M., Verkade, H.J., Wolters, H., Havinga, R., Baller, J., Bloks, V., Müller, M., Sauer, P.J., Kuipers, F. Gastroenterology (2002) [Pubmed]
  4. Postprandial chylomicron formation and fat absorption in multidrug resistance gene 2 P-glycoprotein-deficient mice. Voshol, P.J., Minich, D.M., Havinga, R., Elferink, R.P., Verkade, H.J., Groen, A.K., Kuipers, F. Gastroenterology (2000) [Pubmed]
  5. Regulation of the multidrug resistance protein 2 in the rat liver by lipopolysaccharide and dexamethasone. Kubitz, R., Wettstein, M., Warskulat, U., Häussinger, D. Gastroenterology (1999) [Pubmed]
  6. Cholestasis with altered structure and function of hepatocyte tight junction and decreased expression of canalicular multispecific organic anion transporter in a rat model of colitis. Kawaguchi, T., Sakisaka, S., Mitsuyama, K., Harada, M., Koga, H., Taniguchi, E., Sasatomi, K., Kimura, R., Ueno, T., Sawada, N., Mori, M., Sata, M. Hepatology (2000) [Pubmed]
  7. Taurine supplementation induces multidrug resistance protein 2 and bile salt export pump expression in rats and prevents endotoxin-induced cholestasis. Mühlfeld, A., Kubitz, R., Dransfeld, O., Häussinger, D., Wettstein, M. Arch. Biochem. Biophys. (2003) [Pubmed]
  8. Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liver. Donner, M.G., Keppler, D. Hepatology (2001) [Pubmed]
  9. Role of rat multidrug resistance protein 2 in plasma and biliary disposition of dibromosulfophthalein after microsomal enzyme induction. Johnson, D.R., Klaassen, C.D. Toxicol. Appl. Pharmacol. (2002) [Pubmed]
  10. Biliary excretion of phenolphthalein sulfate in rats. Tanaka, H., Sano, N., Takikawa, H. Pharmacology (2003) [Pubmed]
  11. Regulation of the dynamic localization of the rat Bsep gene-encoded bile salt export pump by anisoosmolarity. Schmitt, M., Kubitz, R., Lizun, S., Wettstein, M., Häussinger, D. Hepatology (2001) [Pubmed]
  12. Asynchronous expression and colocalization of Bsep and Mrp2 during development of rat liver. Zinchuk, V.S., Okada, T., Akimaru, K., Seguchi, H. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  13. Expression and immunolocalization of multidrug resistance protein 2 in rabbit small intestine. Van Aubel, R.A., Hartog, A., Bindels, R.J., Van Os, C.H., Russel, F.G. Eur. J. Pharmacol. (2000) [Pubmed]
  14. Canalicular multispecific organic anion transporter/multidrug resistance protein 2 mediates low-affinity transport of reduced glutathione. Paulusma, C.C., van Geer, M.A., Evers, R., Heijn, M., Ottenhoff, R., Borst, P., Oude Elferink, R.P. Biochem. J. (1999) [Pubmed]
  15. Enhanced expression of basolateral multidrug resistance protein isoforms Mrp3 and Mrp5 in rat liver by LPS. Donner, M.G., Warskulat, U., Saha, N., Häussinger, D. Biol. Chem. (2004) [Pubmed]
  16. Endotoxin downregulates hepatic expression of P-glycoprotein and MRP2 in 2-acetylaminofluorene-treated rats. Tang, W., Yi, C., Kalitsky, J., Piquette-Miller, M. Mol. Cell Biol. Res. Commun. (2000) [Pubmed]
  17. Increase in bile flow and biliary excretion of glutathione-derived sulfhydryls in rats by drug-metabolizing enzyme inducers is mediated by multidrug resistance protein 2. Johnson, D.R., Habeebu, S.S., Klaassen, C.D. Toxicol. Sci. (2002) [Pubmed]
  18. Hepatobiliary excretion of biliverdin isomers and C10-substituted biliverdins in Mrp2-deficient (TR(-)) rats. McDonagh, A.F., Lightner, D.A., Kar, A.K., Norona, W.S. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  19. Electron-microscopic demonstration of multidrug resistance protein 2 (Mrp2) retrieval from the canalicular membrane in response to hyperosmolarity and lipopolysaccharide. Dombrowski, F., Kubitz, R., Chittattu, A., Wettstein, M., Saha, N., Häussinger, D. Biochem. J. (2000) [Pubmed]
  20. Alteration of the expression of adenosine triphosphate-binding cassette transporters associated with bile acid and cholesterol transport in the rat liver and intestine during cholestasis. Kamisako, T., Ogawa, H. J. Gastroenterol. Hepatol. (2005) [Pubmed]
WikiGenes - Universities