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Gene Review

Abcc2  -  ATP-binding cassette, subfamily C...

Rattus norvegicus

Synonyms: ATP-binding cassette sub-family C member 2, Canalicular multidrug resistance protein, Canalicular multispecific organic anion transporter 1, Cmoat, Cmrp, ...
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Disease relevance of Abcc2


High impact information on Abcc2

  • IL-1 beta treatment of primary hepatocytes reduced Mrp2 and RXR alpha expression [6].
  • CONCLUSIONS: Organ-specific regulation of Mrp2 expression in obstructive cholestasis is associated with cytokine-dependent alterations in RAR alpha:RXR alpha nuclear receptors [6].
  • This was temporally associated with down-regulation of liver RAR alpha:RXR alpha nuclear protein levels and binding to the Mrp2 promoter cis element [6].
  • RESULTS: Bsep-expressing Sf9 cell vesicles showed ATP-dependent transport of numerous monoanionic bile salts with similar Michaelis constant values as in cLPM vesicles, whereas several known substrates of the multispecific organic anion transporter Mrp2 were not transported by Bsep [7].
  • In contrast, protein and mRNA expression of both the canalicular ATP-dependent bile salt export pump (Bsep) and the multiorganic anion transporter Mrp2 remained unchanged or were slightly increased during liver regeneration, but also returned to control values 7-14 days after partial hepatectomy [8].

Chemical compound and disease context of Abcc2


Biological context of Abcc2


Anatomical context of Abcc2


Associations of Abcc2 with chemical compounds


Physical interactions of Abcc2

  • Because Mrp3 transports TC and its expression is induced on the basolateral membrane of Mrp2-deficient rats, the enhanced sinusoidal efflux of TC in EHBR may be accounted for, at least partially, by the increased expression of Mrp3 [24].
  • To examine whether P-glycoprotein has a role in canalicular transport of organic anions in addition to the canalicular multispecific organic anion transporter, we studied the effect of colchicine, a vesicular transport inhibitor, and phenothiazine to increase P-glycoprotein expression on biliary excretion of various organic anions in rats [25].

Other interactions of Abcc2

  • In Mrp2-deficient mutant rat liver, the Mrp3 protein expression was most enhanced and its zonation was lost [1].
  • Messenger RNA (mRNA) levels of transporters and binding activities as well as nuclear protein levels of Ntcp, Oatp2, and Mrp2 transactivators were determined 20 to 24 hours later [26].
  • Our data show that in the liver of both strains, exposure to a hypotonic medium stimulates DOX excretion, presumably by activation of P-gp and mrp2 during RVD [27].
  • In contrast, CDF appears to be taken up by Oatp-mediated transport into rat hepatocytes and effluxed via Mrp2 into bile and via Mrp3 into sinusoidal blood [28].
  • Therefore, Bcrp1 has an important role in extruding glucuronide and sulfate conjugates formed in enterocytes into the intestinal lumen, whereas Mrp2 is responsible for the efflux of some glucuronide conjugates [29].

Analytical, diagnostic and therapeutic context of Abcc2

  • Confocal immunohistochemistry showed that Mrp2 expression was confined to the canalicular membrane in both control and pregnant rats and was not detectable in intracellular compartments [19].
  • Western blot studies revealed increased expression of Mrp2 in response to SL whereas AE2 content remained unchanged [30].
  • Enhanced activity and expression of Mrp2 was confirmed by analyzing the excretion rate of dinitrophenyl S-glutathione, an exogenous substrate of Mrp2, in isolated hepatocytes and by immunofluorescence microscopy, respectively [30].
  • SDR liver preperfused with hyperosmolar buffer (405 mosmol/L) for 30 min induced internalization of Mrp2 without changing the basal GSH level, while elimination of hepatic GSH by 300 microM EA perfusion was significantly delayed thereafter [31].
  • After hypophysectomy, Mrp2 mRNA was markedly reduced and the effects of estrogens and testosterone on Mrp2 were prevented, supporting the role of pituitary hormones in controlling Mrp2 expression [32].


  1. Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liver. Donner, M.G., Keppler, D. Hepatology (2001) [Pubmed]
  2. Characterization of organic anion transporter regulation, glutathione metabolism and bile formation in the obese Zucker rat. Geier, A., Dietrich, C.G., Grote, T., Beuers, U., Prüfer, T., Fraunberger, P., Matern, S., Gartung, C., Gerbes, A.L., Bilzer, M. J. Hepatol. (2005) [Pubmed]
  3. Inhibition of transport across the hepatocyte canalicular membrane by the antibiotic fusidate. Bode, K.A., Donner, M.G., Leier, I., Keppler, D. Biochem. Pharmacol. (2002) [Pubmed]
  4. Tienilic acid enhances hyperbilirubinemia in Eisai hyperbilirubinuria rats through hepatic multidrug resistance-associated protein 3 and heme oxygenase-1 induction. Nishiya, T., Kataoka, H., Mori, K., Goto, M., Sugawara, T., Furuhama, K. Toxicol. Sci. (2006) [Pubmed]
  5. 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]
  6. Organ-specific alterations in RAR alpha:RXR alpha abundance regulate rat Mrp2 (Abcc2) expression in obstructive cholestasis. Denson, L.A., Bohan, A., Held, M.A., Boyer, J.L. Gastroenterology (2002) [Pubmed]
  7. Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Stieger, B., Fattinger, K., Madon, J., Kullak-Ublick, G.A., Meier, P.J. Gastroenterology (2000) [Pubmed]
  8. Differential expression of basolateral and canalicular organic anion transporters during regeneration of rat liver. Gerloff, T., Geier, A., Stieger, B., Hagenbuch, B., Meier, P.J., Matern, S., Gartung, C. Gastroenterology (1999) [Pubmed]
  9. Cholestasis and regulation of genes related to drug metabolism and biliary transport in rat liver following treatment with cyclosporine A and sirolimus (Rapamycin). Bramow, S., Ott, P., Thomsen Nielsen, F., Bangert, K., Tygstrup, N., Dalhoff, K. Pharmacol. Toxicol. (2001) [Pubmed]
  10. Impaired activity of the bile canalicular organic anion transporter (Mrp2/cmoat) is not the main cause of ethinylestradiol-induced cholestasis in the rat. Koopen, N.R., Wolters, H., Havinga, R., Vonk, R.J., Jansen, P.L., Müller, M., Kuipers, F. Hepatology (1998) [Pubmed]
  11. Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver. Beuers, U., Bilzer, M., Chittattu, A., Kullak-Ublick, G.A., Keppler, D., Paumgartner, G., Dombrowski, F. Hepatology (2001) [Pubmed]
  12. Retrieval of the mrp2 gene encoded conjugate export pump from the canalicular membrane contributes to cholestasis induced by tert-butyl hydroperoxide and chloro-dinitrobenzene. Schmitt, M., Kubitz, R., Wettstein, M., vom Dahl, S., Häussinger, D. Biol. Chem. (2000) [Pubmed]
  13. Kupffer cell-mediated down regulation of rat hepatic CMOAT/MRP2 gene expression. Nakamura, J., Nishida, T., Hayashi, K., Kawada, N., Ueshima, S., Sugiyama, Y., Ito, T., Sobue, K., Matsuda, H. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  14. Oxidative stress and Mrp2 internalization. Sekine, S., Ito, K., Horie, T. Free Radic. Biol. Med. (2006) [Pubmed]
  15. Cholestatic expression pattern of sinusoidal and canalicular organic anion transport systems in primary cultured rat hepatocytes. Rippin, S.J., Hagenbuch, B., Meier, P.J., Stieger, B. Hepatology (2001) [Pubmed]
  16. Differential regulation of hepatic bile salt and organic anion transporters in pregnant and postpartum rats and the role of prolactin. Cao, J., Huang, L., Liu, Y., Hoffman, T., Stieger, B., Meier, P.J., Vore, M. Hepatology (2001) [Pubmed]
  17. Role of glycosylation in trafficking of Mrp2 in sandwich-cultured rat hepatocytes. Zhang, P., Tian, X., Chandra, P., Brouwer, K.L. Mol. Pharmacol. (2005) [Pubmed]
  18. Cyclosporine interacts with mycophenolic acid by inhibiting the multidrug resistance-associated protein 2. Hesselink, D.A., van Hest, R.M., Mathot, R.A., Bonthuis, F., Weimar, W., de Bruin, R.W., van Gelder, T. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. (2005) [Pubmed]
  19. Expression of rat hepatic multidrug resistance-associated proteins and organic anion transporters in pregnancy. Cao, J., Stieger, B., Meier, P.J., Vore, M. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  20. Characterization of inducible nature of MRP3 in rat liver. Ogawa, K., Suzuki, H., Hirohashi, T., Ishikawa, T., Meier, P.J., Hirose, K., Akizawa, T., Yoshioka, M., Sugiyama, Y. Am. J. Physiol. Gastrointest. Liver Physiol. (2000) [Pubmed]
  21. Metabolism and disposition of gemfibrozil in Wistar and multidrug resistance-associated protein 2-deficient TR- rats. Kim, M.S., Liu, D.Q., Strauss, J.R., Capodanno, I., Yao, Z., Fenyk-Melody, J.E., Franklin, R.B., Vincent, S.H. Xenobiotica (2003) [Pubmed]
  22. 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]
  23. Gender-specific expression of liver organic anion transporters in rat. Rost, D., Kopplow, K., Gehrke, S., Mueller, S., Friess, H., Ittrich, C., Mayer, D., Stiehl, A. Eur. J. Clin. Invest. (2005) [Pubmed]
  24. Sinusoidal efflux of taurocholate is enhanced in Mrp2-deficient rat liver. Akita, H., Suzuki, H., Sugiyama, Y. Pharm. Res. (2001) [Pubmed]
  25. Effects of colchicine and phenothiazine on biliary excretion of organic anions in rats. Takikawa, H., Sano, N., Akimoto, K., Ogasawara, T., Yamanaka, M. J. Gastroenterol. Hepatol. (1998) [Pubmed]
  26. Effects of proinflammatory cytokines on rat organic anion transporters during toxic liver injury and cholestasis. Geier, A., Dietrich, C.G., Voigt, S., Kim, S.K., Gerloff, T., Kullak-Ublick, G.A., Lorenzen, J., Matern, S., Gartung, C. Hepatology (2003) [Pubmed]
  27. Influence of hypotonic stress on the biliary excretion of doxorubicin in Wistar and TR- rats. Gaugg, M., Haslmayer, P., Jäger, W., Thalhammer, T. Anticancer Res. (2001) [Pubmed]
  28. Pharmacokinetics of 5 (and 6)-carboxy-2',7'-dichlorofluorescein and its diacetate promoiety in the liver. Zamek-Gliszczynski, M.J., Xiong, H., Patel, N.J., Turncliff, R.Z., Pollack, G.M., Brouwer, K.L. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  29. Role of breast cancer resistance protein (Bcrp1/Abcg2) in the extrusion of glucuronide and sulfate conjugates from enterocytes to intestinal lumen. Adachi, Y., Suzuki, H., Schinkel, A.H., Sugiyama, Y. Mol. Pharmacol. (2005) [Pubmed]
  30. Mechanisms involved in spironolactone-induced choleresis in the rat. Role of multidrug resistance-associated protein 2. Ruiz, M.L., Villanueva, S.S., Luquita, M.G., Sánchez-Pozzi, E.J., Crocenzi, F.A., Pellegrino, J.M., Ochoa, J.E., Vore, M., Mottino, A.D., Catania, V.A. Biochem. Pharmacol. (2005) [Pubmed]
  31. Ethacrynic-acid-induced glutathione depletion and oxidative stress in normal and Mrp2-deficient rat liver. Ji, B., Ito, K., Sekine, S., Tajima, A., Horie, T. Free Radic. Biol. Med. (2004) [Pubmed]
  32. Hormonal regulation of hepatic multidrug resistance-associated protein 2 (Abcc2) primarily involves the pattern of growth hormone secretion. Simon, F.R., Iwahashi, M., Hu, L.J., Qadri, I., Arias, I.M., Ortiz, D., Dahl, R., Sutherland, E. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
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