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SLCO1B1  -  solute carrier organic anion transporter...

Homo sapiens

 
 
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Disease relevance of SLCO1B1

 

High impact information on SLCO1B1

  • Naturally occurring polymorphisms in OATP1B1, including *5, *9, *15, and *18, were associated with profound loss of activity toward rosuvastatin [6].
  • SHP is a transcriptional repressor that mediates bile acid-induced repression of the bile salt uptake systems rat Ntcp and human OATP-C [7].
  • On the other hand, the LST-1 was only detected in a hepatic cell line [5].
  • Although most of the tested compounds are common substrates of several oatp-related transporters, high-affinity uptake of digoxin is a unique feature of the newly cloned oatp2 [8].
  • They indicate that oatp2 may play an especially important role in the brain accumulation and toxicity of digoxin and in the hepatobiliary and renal excretion of cardiac glycosides from the body [8].
 

Chemical compound and disease context of SLCO1B1

 

Biological context of SLCO1B1

 

Anatomical context of SLCO1B1

  • In the present study, we have established a double-transfected Madin-Darby canine kidney (MDCK II) cell monolayer, which expresses both OATP2 and MRP2 on basal and apical membranes, respectively [15].
  • In OATP2-expressing (zinc-induced) HeLa cells at 37 degrees C, the uptake of [35S]sulfobromophthalein was substantial (51.6 +/- 16.5 pmol/15 min/mg protein, n = 5) with little cell-associated ligand in non-expressing (uninduced) cells (0.54 +/- 0.16 pmol/15 min/mg protein, n = 5, p < 0.002) [16].
  • To investigate the basis of liver-specific expression of OATP-C, we studied promoter function in the two hepatocyte-derived cell lines HepG2 and Huh7 and in nonhepatic HeLa cells [17].
  • Expression of OATP-A and OATP-C was not detected in any of the keratinocyte samples [18].
  • Furthermore, Oatp2 is strongly expressed at the rat blood-brain barrier (BBB) [19].
 

Associations of SLCO1B1 with chemical compounds

  • Overall, 2-5% of individuals in various populations may be expected to show markedly elevated plasma pravastatin concentrations due to the SLCO1B1 polymorphism [12].
  • Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6 [1].
  • The basal-to-apical transport of 17 beta estradiol 17 beta-d-glucuronide (E(2)17 beta G), pravastatin, and leukotriene C(4) (LTC(4)), which are substrates of OATP2 and MRP2, was significantly higher than that in the opposite direction in the double-transfected cells [15].
  • In contrast, basal-to-apical transport of estrone-3-sulfate and dehydroepiandrosterone sulfate, which are significantly transported by OATP2, but not by MRP2, was not stimulated by MRP2 expression [15].
  • Additional inhibitors of phalloidin uptake mediated by SLC21A6 included the immunosuppressive drugs cyclosporin A, FK506, and rapamycin, whereas alpha-amanitin was only a weak inhibitor [20].
 

Physical interactions of SLCO1B1

 

Other interactions of SLCO1B1

  • The corresponding K(i) values were 17 micromol/L for OATP-C, 5 micromol/L for OATP8, and 51 micromol/L for OATP-A [22].
  • Approximate K(i) values were 2 micromol/L for OATP-C, 3 micromol/L for OATP8, 3 micromol/L for OATP-B and 11 micromol/L for OATP-A [22].
  • In rats, rifamycin SV and rifampicin were shown to interfere with hepatic organic anion uptake by inhibition of the organic anion transporting polypeptides Oatp1 and Oatp2 [22].
  • The double-transfected MDCK II monolayer expressing both OATP2 and MRP2 may be used to analyze the hepatic vectorial transport of organic anions and to screen the transport profiles of new drug candidates [15].
  • There were no differences in frequencies of SLCO1B1, MDR1, and CYP3A5 polymorphisms between the 2 groups [23].
 

Analytical, diagnostic and therapeutic context of SLCO1B1

References

  1. Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6. Cui, Y., König, J., Leier, I., Buchholz, U., Keppler, D. J. Biol. Chem. (2001) [Pubmed]
  2. Detection of the human organic anion transporters SLC21A6 (OATP2) and SLC21A8 (OATP8) in liver and hepatocellular carcinoma. Cui, Y., König, J., Nies, A.T., Pfannschmidt, M., Hergt, M., Franke, W.W., Alt, W., Moll, R., Keppler, D. Lab. Invest. (2003) [Pubmed]
  3. A novel variant allele of OATP-C (SLCO1B1) found in a Japanese patient with pravastatin-induced myopathy. Morimoto, K., Oishi, T., Ueda, S., Ueda, M., Hosokawa, M., Chiba, K. Drug Metab. Pharmacokinet. (2004) [Pubmed]
  4. Molecular characterization and functional regulation of a novel rat liver-specific organic anion transporter rlst-1. Kakyo, M., Unno, M., Tokui, T., Nakagomi, R., Nishio, T., Iwasashi, H., Nakai, D., Seki, M., Suzuki, M., Naitoh, T., Matsuno, S., Yawo, H., Abe, T. Gastroenterology (1999) [Pubmed]
  5. LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Abe, T., Unno, M., Onogawa, T., Tokui, T., Kondo, T.N., Nakagomi, R., Adachi, H., Fujiwara, K., Okabe, M., Suzuki, T., Nunoki, K., Sato, E., Kakyo, M., Nishio, T., Sugita, J., Asano, N., Tanemoto, M., Seki, M., Date, F., Ono, K., Kondo, Y., Shiiba, K., Suzuki, M., Ohtani, H., Shimosegawa, T., Iinuma, K., Nagura, H., Ito, S., Matsuno, S. Gastroenterology (2001) [Pubmed]
  6. Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Ho, R.H., Tirona, R.G., Leake, B.F., Glaeser, H., Lee, W., Lemke, C.J., Wang, Y., Kim, R.B. Gastroenterology (2006) [Pubmed]
  7. Enterohepatic bile salt transporters in normal physiology and liver disease. Kullak-Ublick, G.A., Stieger, B., Meier, P.J. Gastroenterology (2004) [Pubmed]
  8. Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain. Noé, B., Hagenbuch, B., Stieger, B., Meier, P.J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  9. Involvement of organic anion transporting polypeptides in the transport of troglitazone sulfate: implications for understanding troglitazone hepatotoxicity. Nozawa, T., Sugiura, S., Nakajima, M., Goto, A., Yokoi, T., Nezu, J., Tsuji, A., Tamai, I. Drug Metab. Dispos. (2004) [Pubmed]
  10. Uptake of enalapril and expression of organic anion transporting polypeptide 1 in zonal, isolated rat hepatocytes. Abu-Zahra, T.N., Wolkoff, A.W., Kim, R.B., Pang, K.S. Drug Metab. Dispos. (2000) [Pubmed]
  11. Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells. Lu, W.J., Tamai, I., Nezu, J., Lai, M.L., Huang, J.D. J. Biomed. Sci. (2006) [Pubmed]
  12. Influence of drug transporter polymorphisms on pravastatin pharmacokinetics in humans. Kivist??, K.T., Niemi, M. Pharm. Res. (2007) [Pubmed]
  13. Effect of SLCO1B1 polymorphism on induction of CYP3A4 by rifampicin. Niemi, M., Kivistö, K.T., Diczfalusy, U., Bodin, K., Bertilsson, L., Fromm, M.F., Eichelbaum, M. Pharmacogenet. Genomics (2006) [Pubmed]
  14. Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide. König, J., Cui, Y., Nies, A.T., Keppler, D. J. Biol. Chem. (2000) [Pubmed]
  15. Transcellular transport of organic anions across a double-transfected Madin-Darby canine kidney II cell monolayer expressing both human organic anion-transporting polypeptide (OATP2/SLC21A6) and Multidrug resistance-associated protein 2 (MRP2/ABCC2). Sasaki, M., Suzuki, H., Ito, K., Abe, T., Sugiyama, Y. J. Biol. Chem. (2002) [Pubmed]
  16. The human organic anion transport protein SLC21A6 is not sufficient for bilirubin transport. Wang, P., Kim, R.B., Chowdhury, J.R., Wolkoff, A.W. J. Biol. Chem. (2003) [Pubmed]
  17. Characterization of the human OATP-C (SLC21A6) gene promoter and regulation of liver-specific OATP genes by hepatocyte nuclear factor 1 alpha. Jung, D., Hagenbuch, B., Gresh, L., Pontoglio, M., Meier, P.J., Kullak-Ublick, G.A. J. Biol. Chem. (2001) [Pubmed]
  18. Active influx transport is mediated by members of the organic anion transporting polypeptide family in human epidermal keratinocytes. Schiffer, R., Neis, M., Höller, D., Rodríguez, F., Geier, A., Gartung, C., Lammert, F., Dreuw, A., Zwadlo-Klarwasser, G., Merk, H., Jugert, F., Baron, J.M. J. Invest. Dermatol. (2003) [Pubmed]
  19. Organic anion-transporting polypeptides mediate transport of opioid peptides across blood-brain barrier. Gao, B., Hagenbuch, B., Kullak-Ublick, G.A., Benke, D., Aguzzi, A., Meier, P.J. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  20. Characterization of the transport of the bicyclic peptide phalloidin by human hepatic transport proteins. Fehrenbach, T., Cui, Y., Faulstich, H., Keppler, D. Naunyn Schmiedebergs Arch. Pharmacol. (2003) [Pubmed]
  21. Clinical pharmacokinetics of atorvastatin. Lennernäs, H. Clinical pharmacokinetics. (2003) [Pubmed]
  22. Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver. Vavricka, S.R., Van Montfoort, J., Ha, H.R., Meier, P.J., Fattinger, K. Hepatology (2002) [Pubmed]
  23. Exposure of atorvastatin is unchanged but lactone and acid metabolites are increased several-fold in patients with atorvastatin-induced myopathy. Hermann, M., Bogsrud, M.P., Molden, E., Asberg, A., Mohebi, B.U., Ose, L., Retterstøl, K. Clin. Pharmacol. Ther. (2006) [Pubmed]
  24. The human organic anion transporting polypeptide 8 (SLCO1B3) gene is transcriptionally repressed by hepatocyte nuclear factor 3beta in hepatocellular carcinoma. Vavricka, S.R., Jung, D., Fried, M., Grützner, U., Meier, P.J., Kullak-Ublick, G.A. J. Hepatol. (2004) [Pubmed]
  25. Disposition and sterol-lowering effect of ezetimibe are influenced by single-dose coadministration of rifampin, an inhibitor of multidrug transport proteins. Oswald, S., Giessmann, T., Luetjohann, D., Wegner, D., Rosskopf, D., Weitschies, W., Siegmund, W. Clin. Pharmacol. Ther. (2006) [Pubmed]
  26. Pharmacokinetics and response to pravastatin in paediatric patients with familial hypercholesterolaemia and in paediatric cardiac transplant recipients in relation to polymorphisms of the SLCO1B1 and ABCB1 genes. Hedman, M., Antikainen, M., Holmberg, C., Neuvonen, M., Eichelbaum, M., Kivistö, K.T., Neuvonen, P.J., Niemi, M. British journal of clinical pharmacology. (2006) [Pubmed]
  27. Simvastatin does not influence the intestinal P-glycoprotein and MPR2, and the disposition of talinolol after chronic medication in healthy subjects genotyped for the ABCB1, ABCC2 and SLCO1B1 polymorphisms. Bernsdorf, A., Giessmann, T., Modess, C., Wegner, D., Igelbrink, S., Hecker, U., Haenisch, S., Cascorbi, I., Terhaag, B., Siegmund, W. British journal of clinical pharmacology. (2006) [Pubmed]
 
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