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Gene Review

Slco1a2  -  solute carrier organic anion transporter...

Rattus norvegicus

Synonyms: Brain digoxin carrier protein, Brain-specific organic anion transporter, OATP-B1, Oatp1a4, Oatp2, ...
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Disease relevance of Slco1a4

  • CONCLUSIONS: Oatp2 and Mrp2 expression is decreased in fatty liver and may impair metabolism and biliary secretion of numerous xenobiotics [1].

High impact information on Slco1a4

  • CONCLUSIONS: These results provide definite evidence for the partially overlapping and partially selective substrate specificities of Oatp1 and Oatp2 [2].
  • We postulated that increased uptake of cardiac glycosides observed after pretreatment of animals with phenobarbital (PB) and pregnenolone-16alpha-carbonitrile (PCN) occurs via increased hepatic expression of Oatp1 and/or Oatp2 [3].
  • To determine the temporal effects of PCN treatment on the expression of Oatp2, rats were administered PCN, livers were extracted at various times, and Oatp2 expression was analyzed [3].
  • These results suggest that Oatp2, but not Oatp1, is inducible by PB and PCN, which imparts the increased capacity of the liver to extract cardiac glycosides from the plasma [3].
  • Organic anion transporting polypeptide 2 (Oatp2) mRNA was decreased in pregnancy and increased postpartum, but changes in Oatp2 protein were not significant [4].

Biological context of Slco1a4


Anatomical context of Slco1a4


Associations of Slco1a4 with chemical compounds

  • The finding that Oatp2 expression increases in response to PB and PCN is consistent with our previous findings that PB and PCN enhance hepatic uptake of cardiac glycosides [3].
  • Digoxin specifically inhibited the transport via Oatp2 (K(i) = 0.037 microM) [12].
  • Probenecid had a similar affinity for these transporters (Oatp1, Oatp2, Oat1, and Oat3) examined in this study [12].
  • Methods: The inhibitory effects of 20 compounds on the Oatpl-mediated transport of estradiol 17beta-D-glucuronide and on the Oatp2-mediated transport of digoxin were examined in cDNA-transfected LLC-PK1cells [10].
  • The Ki values of ibuprofen and quinidine were estimated to be 19 and 13 times lower for Oatpl compared with Oatp2, whereas the values for rifampicin, quinine, and digoxin were 13, 20, and 100< times lower for Oatp2 compared with Oatpl [10].

Regulatory relationships of Slco1a4


Other interactions of Slco1a4


Analytical, diagnostic and therapeutic context of Slco1a4


  1. 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]
  2. Localization and function of the organic anion-transporting polypeptide Oatp2 in rat liver. Reichel, C., Gao, B., Van Montfoort, J., Cattori, V., Rahner, C., Hagenbuch, B., Stieger, B., Kamisako, T., Meier, P.J. Gastroenterology (1999) [Pubmed]
  3. Differential effects of microsomal enzyme-inducing chemicals on the hepatic expression of rat organic anion transporters, OATP1 and OATP2. Rausch-Derra, L.C., Hartley, D.P., Meier, P.J., Klaassen, C.D. Hepatology (2001) [Pubmed]
  4. 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]
  5. 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]
  6. Functional characterization of the mouse organic-anion-transporting polypeptide 2. van Montfoort, J.E., Schmid, T.E., Adler, I.D., Meier, P.J., Hagenbuch, B. Biochim. Biophys. Acta (2002) [Pubmed]
  7. Rifamycin SV and rifampicin exhibit differential inhibition of the hepatic rat organic anion transporting polypeptides, Oatp1 and Oatp2. Fattinger, K., Cattori, V., Hagenbuch, B., Meier, P.J., Stieger, B. Hepatology (2000) [Pubmed]
  8. Role of organic anion transporting polypeptide 2 in pharmacokinetics of digoxin and beta-methyldigoxin in rats. Funakoshi, S., Murakami, T., Yumoto, R., Kiribayashi, Y., Takano, M. Journal of pharmaceutical sciences. (2005) [Pubmed]
  9. Functional characterization of rat brain-specific organic anion transporter (Oatp14) at the blood-brain barrier: high affinity transporter for thyroxine. Sugiyama, D., Kusuhara, H., Taniguchi, H., Ishikawa, S., Nozaki, Y., Aburatani, H., Sugiyama, Y. J. Biol. Chem. (2003) [Pubmed]
  10. Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport. Shitara, Y., Sugiyama, D., Kusuhara, H., Kato, Y., Abe, T., Meier, P.J., Itoh, T., Sugiyama, Y. Pharm. Res. (2002) [Pubmed]
  11. Localization of the organic anion transporting polypeptide 2 (Oatp2) in capillary endothelium and choroid plexus epithelium of rat brain. Gao, B., Stieger, B., Noé, B., Fritschy, J.M., Meier, P.J. J. Histochem. Cytochem. (1999) [Pubmed]
  12. Characterization of the efflux transport of 17beta-estradiol-D-17beta-glucuronide from the brain across the blood-brain barrier. Sugiyama, D., Kusuhara, H., Shitara, Y., Abe, T., Meier, P.J., Sekine, T., Endou, H., Suzuki, H., Sugiyama, Y. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
  13. Hepatic uptake of synthetic chlorogenic acid derivatives by the organic anion transport proteins. Schwab, D., Herling, A.W., Hemmerle, H., Schubert, G., Hagenbuch, B., Burger, H.J. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
  14. Hepatobiliary organic anion transporters are differentially regulated in acute toxic liver injury induced by carbon tetrachloride. Geier, A., Kim, S.K., Gerloff, T., Dietrich, C.G., Lammert, F., Karpen, S.J., Stieger, B., Meier, P.J., Matern, S., Gartung, C. J. Hepatol. (2002) [Pubmed]
  15. Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3. Cattori, V., van Montfoort, J.E., Stieger, B., Landmann, L., Meijer, D.K., Winterhalter, K.H., Meier, P.J., Hagenbuch, B. Pflugers Arch. (2001) [Pubmed]
  16. 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]
  17. Activators of the rat pregnane X receptor differentially modulate hepatic and intestinal gene expression. Hartley, D.P., Dai, X., He, Y.D., Carlini, E.J., Wang, B., Huskey, S.E., Ulrich, R.G., Rushmore, T.H., Evers, R., Evans, D.C. Mol. Pharmacol. (2004) [Pubmed]
  18. Vascular binding, blood flow, transporter, and enzyme interactions on the processing of digoxin in rat liver. Liu, L., Mak, E., Tirona, R.G., Tan, E., Novikoff, P.M., Wang, P., Wolkoff, A.W., Pang, K.S. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  19. Regulation of basolateral organic anion transporters in ethinylestradiol-induced cholestasis in the rat. Geier, A., Dietrich, C.G., Gerloff, T., Haendly, J., Kullak-Ublick, G.A., Stieger, B., Meier, P.J., Matern, S., Gartung, C. Biochim. Biophys. Acta (2003) [Pubmed]
  20. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters the mRNA expression of critical genes associated with cholesterol metabolism, bile acid biosynthesis, and bile transport in rat liver: a microarray study. Fletcher, N., Wahlström, D., Lundberg, R., Nilsson, C.B., Nilsson, K.C., Stockling, K., Hellmold, H., Håkansson, H. Toxicol. Appl. Pharmacol. (2005) [Pubmed]
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