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)
 

Links

 

Gene Review

SLCO1A2  -  solute carrier organic anion transporter...

Homo sapiens

Synonyms: OATP, OATP-1, OATP-A, OATP1, OATP1A2, ...
 
 
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 SLCO1A2

  • At the protein level, however, only OATP1A2 and OATP2B1 were detectable by immunofluorescence microscopy in the luminal membrane of endothelial cells forming the blood-brain barrier and the blood-tumor barrier, but not in the glioma cells [1].
  • Because of its expression on the apical membrane of the distal tubule and in tissues relevant to MTX disposition and toxicity, these findings suggest that OATP1A2 may play a role in active tubular reabsorption of MTX and in MTX-induced toxicities [2].
  • We investigated the influence of intracellular pH (pHi) on [14C]-glycocholate (GC) uptake by human hepatoblastoma HepG2 cells that express sodium-independent (mainly OATP-A and OATP-8), but not sodium-dependent, GC transporters [3].
  • However, enalapril was not taken up by Oatp2 nor by the human OATP expressed in recombinant vaccinia systems [4].
 

High impact information on SLCO1A2

  • Expression of the apical sodium-dependent bile acid transporter (ASBT) and of the organic anion transporting polypeptide (OATP-A) was detected and associated with sodium-dependent and sodium-independent [(3)H]taurocholate uptake in BEC [5].
  • Using real time quantitative reverse transcription-PCR, the absolute abundance of OATP-A/1A2, OATP-C/1B1, and OATP8/1B3 mRNA in human liver biopsies was measured [6].
  • SLCO/OATP-like Transport of Glutathione in FasL-induced Apoptosis: GLUTATHIONE EFFLUX IS COUPLED TO AN ORGANIC ANION EXCHANGE AND IS NECESSARY FOR THE PROGRESSION OF THE EXECUTION PHASE OF APOPTOSIS [7].
  • Together these results suggest that GSH efflux during FasL-induced apoptosis is mediated by a SLCO/OATP-like transport mechanism that modulates the progression of the execution phase of apoptosis [7].
  • Therefore, genetic variation in SLCO1A2 may have important implications to the disposition and tissue penetration of substrate drugs [8].
 

Biological context of SLCO1A2

 

Anatomical context of SLCO1A2

  • Taken together, these data suggest that SLCO1A2 polymorphisms may be an important yet unrecognized contributor to inter-individual variability in drug disposition and central nervous system entry of substrate drugs [8].
  • The broad substrate spectrum covered by the three hepatocellular OATP transporters enables representative analyses of the uptake of many organic anions into human hepatocytes [11].
  • Expression of OATP-A and OATP-C was not detected in any of the keratinocyte samples [12].
  • Furthermore, with the Xenopus laevis oocyte system the delta-opioid receptor agonists [D-penicillamine(2,5)]enkephalin (DPDPE) and deltorphin II were identified as new transport substrates of OATP-A [13].
  • These data imply CNT3 may play a specialized role in nucleoside accumulation in milk and may identify an important role for PEPT2 and OATP-A transporters at the lactating mammary epithelium [14].
 

Associations of SLCO1A2 with chemical compounds

  • These results demonstrate that OATP-A can mediate transport of the analgesic opioid peptides DPDPE and deltorphin II across the human BBB [13].
  • Among the tested Oatps/OATPs, rat Oatp1b2, human OATP1B1, human OATP1B3, and human OATP1A2 transported microcystin-LR 2- to 5-fold above water-injected control oocytes [15].
  • While GF120918, a specific inhibitor of P-gp, and MK571, a MRP transporter family inhibitor, significantly enhanced SQV uptake, estrone 3-sulfate, a substrate of OATP-A, significantly inhibited SQV uptake by Hep G2 cells [16].
  • In the present study, we demonstrate OATP1A2 protein expression in human brain capillary and renal distal nephron using immunohistochemistry [8].
  • Four protein-altering variants in OATP1A2 exhibited altered transport of ES and/or MTX [2].
 

Other interactions of SLCO1A2

  • This study localizes the human OATP (now called OATP-A; SLC21A3) at the BBB in humans [13].
  • However, for human OATPs additional regional differences in expression were found with OATP1A2 and OATP1C1 being expressed only in the pars plana of human ciliary body epithelium [17].
  • Here we show that L1 ASP is capable of functioning as an alternative promoter, giving rise to a chimeric transcript whose coding region is identical to the ORF of mRNA of the following genes: KIAA1797, CLCN5, and SLCO1A2 [18].

References

  1. ABCC drug efflux pumps and organic anion uptake transporters in human gliomas and the blood-tumor barrier. Bronger, H., König, J., Kopplow, K., Steiner, H.H., Ahmadi, R., Herold-Mende, C., Keppler, D., Nies, A.T. Cancer Res. (2005) [Pubmed]
  2. Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and its genetic variants. Badagnani, I., Castro, R.A., Taylor, T.R., Brett, C.M., Huang, C.C., Stryke, D., Kawamoto, M., Johns, S.J., Ferrin, T.E., Carlson, E.J., Burchard, E.G., Giacomini, K.M. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  3. Sensitivity of bile acid transport by organic anion-transporting polypeptides to intracellular pH. Marin, J.J., Mangas, D., Martinez-Diez, M.C., El-Mir, M.Y., Briz, O., Serrano, M.A. Biochim. Biophys. Acta (2003) [Pubmed]
  4. 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]
  5. Bile acid transport and regulating functions in the human biliary epithelium. Chignard, N., Mergey, M., Veissière, D., Parc, R., Capeau, J., Poupon, R., Paul, A., Housset, C. Hepatology (2001) [Pubmed]
  6. OATP8/1B3-mediated Cotransport of Bile Acids and Glutathione: AN EXPORT PATHWAY FOR ORGANIC ANIONS FROM HEPATOCYTES? Briz, O., Romero, M.R., Martinez-Becerra, P., Macias, R.I., Perez, M.J., Jimenez, F., Martin, F.G., Marin, J.J. J. Biol. Chem. (2006) [Pubmed]
  7. SLCO/OATP-like Transport of Glutathione in FasL-induced Apoptosis: GLUTATHIONE EFFLUX IS COUPLED TO AN ORGANIC ANION EXCHANGE AND IS NECESSARY FOR THE PROGRESSION OF THE EXECUTION PHASE OF APOPTOSIS. Franco, R., Cidlowski, J.A. J. Biol. Chem. (2006) [Pubmed]
  8. Polymorphisms in human organic anion-transporting polypeptide 1A2 (OATP1A2): implications for altered drug disposition and central nervous system drug entry. Lee, W., Glaeser, H., Smith, L.H., Roberts, R.L., Moeckel, G.W., Gervasini, G., Leake, B.F., Kim, R.B. J. Biol. Chem. (2005) [Pubmed]
  9. Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: possible role of organic anion transporting polypeptides. Dresser, G.K., Kim, R.B., Bailey, D.G. Clin. Pharmacol. Ther. (2005) [Pubmed]
  10. Pharmacogenomics of the OATP and OAT families. Marzolini, C., Tirona, R.G., Kim, R.B. Pharmacogenomics (2004) [Pubmed]
  11. Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells. Kopplow, K., Letschert, K., König, J., Walter, B., Keppler, D. Mol. Pharmacol. (2005) [Pubmed]
  12. 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]
  13. 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]
  14. Transporter gene expression in lactating and nonlactating human mammary epithelial cells using real-time reverse transcription-polymerase chain reaction. Alcorn, J., Lu, X., Moscow, J.A., McNamara, P.J. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  15. Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin. Fischer, W.J., Altheimer, S., Cattori, V., Meier, P.J., Dietrich, D.R., Hagenbuch, B. Toxicol. Appl. Pharmacol. (2005) [Pubmed]
  16. Human organic anion-transporting polypeptide OATP-A (SLC21A3) acts in concert with P-glycoprotein and multidrug resistance protein 2 in the vectorial transport of Saquinavir in Hep G2 cells. Su, Y., Zhang, X., Sinko, P.J. Mol. Pharm. (2004) [Pubmed]
  17. Localization of organic anion transporting polypeptides in the rat and human ciliary body epithelium. Gao, B., Huber, R.D., Wenzel, A., Vavricka, S.R., Ismair, M.G., Remé, C., Meier, P.J. Exp. Eye Res. (2005) [Pubmed]
  18. L1 antisense promoter drives tissue-specific transcription of human genes. Mätlik, K., Redik, K., Speek, M. J. Biomed. Biotechnol. (2006) [Pubmed]
 
WikiGenes - Universities