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

SLC22A1  -  solute carrier family 22 (organic cation...

Homo sapiens

Synonyms: HOCT1, OCT1, Organic cation transporter 1, Solute carrier family 22 member 1, hOCT1, ...
 
 
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 SLC22A1

  • Analysis of octamer-binding transcription factors Oct2 and Oct1 and their coactivator BOB.1/OBF.1 in lymphomas [1].
  • These data suggest that HIV protease inhibitors are potent inhibitors, but poor substrates, of hOCT1 [2].
 

High impact information on SLC22A1

  • OBF1 alleviates DNA sequence requirements of the Oct1 dimer on PORE-related sequences in vitro [3].
  • Furthermore, OBF1 stabilizes POU dimer-DNA interactions and overrides Oct1 interface mutations, which abolish PORE-mediated dimerization without OBF1 [3].
  • These mutations either abolished (AP-2 and HES-1) or created (Oct1) transcription-factor binding sites involved in the development and differentiation of neuronal systems [4].
  • To understand the genetic basis of extensive interindividual differences in xenobiotic disposition, we functionally characterized 15 protein-altering variants of the human liver organic cation transporter, OCT1, in Xenopus oocytes [5].
  • Because OCT1 interacts with a variety of structurally diverse organic cations, including clinically used drugs as well as toxic substances (e.g., N-methylpyridinium, MPP(+)), it is an important determinant of systemic exposure to many xenobiotics [5].
 

Chemical compound and disease context of SLC22A1

  • In cis-inhibition studies, all of the HIV protease inhibitors tested, i.e., indinavir (IC(50) of 62 microM), nelfinavir (IC(50) of 22 microM), ritonavir (IC(50) of 5.2 microM), and saquinavir (IC(50) of 8.3 microM) inhibited TEA uptake in HeLa cells expressing hOCT1 [2].
 

Biological context of SLC22A1

  • Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions [6].
  • The two human organic cation transporter genes SLC22A1 and SLC22A2 are located on chromosome 6q26 [7].
  • Thus, hOCT1, which is expressed in the intestine and liver, is likely to play a major role in the intestinal absorption and hepatic disposition of ranitidine and famotidine in humans, whereas hOCT2, the major isoform present in the kidney, may play only a minor role in their renal elimination [8].
  • Ranitidine and famotidine exhibited similarly potent inhibition of [3H]1-methyl-4-phenyl pyridinium uptake into hOCT1-expressing (IC50= 33 and 28 microM, respectively) and hOCT2-expressing oocytes (IC50= 76 and 114 microM, respectively) [8].
  • The data show that OCT1 and OCT2 mediate luminal ACh release in human airways and suggest that ACh release is blocked after inhalation of budesonide [9].
 

Anatomical context of SLC22A1

  • In Caco-2 cells, the mRNA of all three hOCT and the proteins hOCT2 and hOCT3 were detected [10].
  • More importantly, immunocytochemical analyses of human jejunum revealed for the first time that hOCT3 is localized to the brush border membrane whereas hOCT1 immunolabeling was mainly observed at the lateral membranes of the enterocytes [10].
  • Using immunohistochemistry in rats and humans, OCT1, OCT2, and OCT3 were localized to the luminal membrane of ciliated epithelial cells [9].
  • Interaction of cis-platin with hOCT2 in kidney or hOCT1 in liver was investigated with the fluorescent cation 4-[4-(dimethyl-amino)styril]-methylpyridinium in stably transfected HEK293 cells and for the first time in tissues physiologically expressing these transporters, human proximal tubules, and human hepatocyte couplets [11].
  • Incubation of a labeled oligonucleotide probe encompassing the -73/-68 GC box and -64/-57 Oct1-binding site with a nuclear extract from drug-treated KB cells yielded higher levels of the specific DNA-protein complex than an extract of untreated cells [12].
 

Associations of SLC22A1 with chemical compounds

  • However, oxaliplatin showed almost no influence on the TEA uptakes in the HEK293 cells expressing hOCT1, hOCT2, and hOCT3 [13].
  • When stably expressed in human embryonic kidney (HEK293) cells, only the full length hOCT1 cDNA mediated decynium-22 (D22)-sensitive uptake of tritiated 1-methyl-4-phenylpyridinium ([3H]-MPP+) [14].
  • Influx transporters such as OCT1, OATP-B, and OATP8 were repressed by PB and TCDD [15].
  • Differential expression of influx (hOCT1) and efflux (MDR1) transporters may be a critical determinant of intracellular drug levels and, hence, resistance to imatinib [16].
  • In addition, the bile acid taurocholate inhibited the uptake of 3H-MPP+ in oocytes expressing hOCT1 [17].
 

Other interactions of SLC22A1

  • SLC22A1 and SLC22A2 localized to the same locus, demonstrating the conservation of the close physical linkage of these three organic cation transporter genes in mouse and human [18].
  • Corticosterone and O-methylisoprenaline (1 microM each), but not desipramine, inhibited NE uptake, a profile indicative of NE uptake by EMT, but not OCT-1 [19].
  • On the other hand, the DNA topoisomerase II inhibitor, TAS-103, strongly induced promoter activity, and this effect was completely eradicated when a mutation was introduced into the Oct1-binding site [12].
 

Analytical, diagnostic and therapeutic context of SLC22A1

References

  1. Analysis of octamer-binding transcription factors Oct2 and Oct1 and their coactivator BOB.1/OBF.1 in lymphomas. Sáez, A.I., Artiga, M.J., Sánchez-Beato, M., Sánchez-Verde, L., García, J.F., Camacho, F.I., Franco, R., Piris, M.A. Mod. Pathol. (2002) [Pubmed]
  2. Interactions of HIV protease inhibitors with a human organic cation transporter in a mammalian expression system. Zhang, L., Gorset, W., Washington, C.B., Blaschke, T.F., Kroetz, D.L., Giacomini, K.M. Drug Metab. Dispos. (2000) [Pubmed]
  3. OBF1 enhances transcriptional potential of Oct1. Lins, K., Reményi, A., Tomilin, A., Massa, S., Wilmanns, M., Matthias, P., Schöler, H.R. EMBO J. (2003) [Pubmed]
  4. Promoter mutations that increase amyloid precursor-protein expression are associated with Alzheimer disease. Theuns, J., Brouwers, N., Engelborghs, S., Sleegers, K., Bogaerts, V., Corsmit, E., De Pooter, T., van Duijn, C.M., De Deyn, P.P., Van Broeckhoven, C. Am. J. Hum. Genet. (2006) [Pubmed]
  5. Evolutionary conservation predicts function of variants of the human organic cation transporter, OCT1. Shu, Y., Leabman, M.K., Feng, B., Mangravite, L.M., Huang, C.C., Stryke, D., Kawamoto, M., Johns, S.J., DeYoung, J., Carlson, E., Ferrin, T.E., Herskowitz, I., Giacomini, K.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  6. Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions. Sakata, T., Anzai, N., Shin, H.J., Noshiro, R., Hirata, T., Yokoyama, H., Kanai, Y., Endou, H. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  7. The two human organic cation transporter genes SLC22A1 and SLC22A2 are located on chromosome 6q26. Koehler, M.R., Wissinger, B., Gorboulev, V., Koepsell, H., Schmid, M. Cytogenet. Cell Genet. (1997) [Pubmed]
  8. Differential substrate and inhibitory activities of ranitidine and famotidine toward human organic cation transporter 1 (hOCT1; SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3). Bourdet, D.L., Pritchard, J.B., Thakker, D.R. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  9. Polyspecific cation transporters mediate luminal release of acetylcholine from bronchial epithelium. Lips, K.S., Volk, C., Schmitt, B.M., Pfeil, U., Arndt, P., Miska, D., Ermert, L., Kummer, W., Koepsell, H. Am. J. Respir. Cell Mol. Biol. (2005) [Pubmed]
  10. Drug specificity and intestinal membrane localization of human organic cation transporters (OCT). Müller, J., Lips, K.S., Metzner, L., Neubert, R.H., Koepsell, H., Brandsch, M. Biochem. Pharmacol. (2005) [Pubmed]
  11. Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Ciarimboli, G., Ludwig, T., Lang, D., Pavenstädt, H., Koepsell, H., Piechota, H.J., Haier, J., Jaehde, U., Zisowsky, J., Schlatter, E. Am. J. Pathol. (2005) [Pubmed]
  12. Enhanced expression of the human vacuolar H+-ATPase c subunit gene (ATP6L) in response to anticancer agents. Torigoe, T., Izumi, H., Ishiguchi, H., Uramoto, H., Murakami, T., Ise, T., Yoshida, Y., Tanabe, M., Nomoto, M., Itoh, H., Kohno, K. J. Biol. Chem. (2002) [Pubmed]
  13. Cisplatin and Oxaliplatin, but Not Carboplatin and Nedaplatin, Are Substrates for Human Organic Cation Transporters (SLC22A1-3 and Multidrug and Toxin Extrusion Family). Yonezawa, A., Masuda, S., Yokoo, S., Katsura, T., Inui, K. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  14. Molecular cloning, functional characterization and genomic organization of four alternatively spliced isoforms of the human organic cation transporter 1 (hOCT1/SLC22A1). Hayer, M., Bönisch, H., Brüss, M. Ann. Hum. Genet. (1999) [Pubmed]
  15. Differential regulation of sinusoidal and canalicular hepatic drug transporter expression by xenobiotics activating drug-sensing receptors in primary human hepatocytes. Jigorel, E., Le Vee, M., Boursier-Neyret, C., Parmentier, Y., Fardel, O. Drug Metab. Dispos. (2006) [Pubmed]
  16. Active transport of imatinib into and out of cells: implications for drug resistance. Thomas, J., Wang, L., Clark, R.E., Pirmohamed, M. Blood (2004) [Pubmed]
  17. Cloning and functional expression of a human liver organic cation transporter. Zhang, L., Dresser, M.J., Gray, A.T., Yost, S.C., Terashita, S., Giacomini, K.M. Mol. Pharmacol. (1997) [Pubmed]
  18. Cloning of the mouse and human solute carrier 22a3 (Slc22a3/SLC22A3) identifies a conserved cluster of three organic cation transporters on mouse chromosome 17 and human 6q26-q27. Verhaagh, S., Schweifer, N., Barlow, D.P., Zwart, R. Genomics (1999) [Pubmed]
  19. Norepinephrine transport by the extraneuronal monoamine transporter in human bronchial arterial smooth muscle cells. Horvath, G., Sutto, Z., Torbati, A., Conner, G.E., Salathe, M., Wanner, A. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  20. The Human Organic Cation Transporter-1 Gene Is Transactivated by Hepatocyte Nuclear Factor-4{alpha}. Saborowski, M., Kullak-Ublick, G.A., Eloranta, J.J. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  21. Cloning and characterization of two human polyspecific organic cation transporters. Gorboulev, V., Ulzheimer, J.C., Akhoundova, A., Ulzheimer-Teuber, I., Karbach, U., Quester, S., Baumann, C., Lang, F., Busch, A.E., Koepsell, H. DNA Cell Biol. (1997) [Pubmed]
  22. Enantioselective binding to the human organic cation transporter-1 (hOCT1) determined using an immobilized hOCT1 liquid chromatographic stationary phase. Moaddel, R., Patel, S., Jozwiak, K., Yamaguchi, R., Ho, P.C., Wainer, I.W. Chirality. (2005) [Pubmed]
 
WikiGenes - Universities