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Slc22a1  -  solute carrier family 22 (organic cation...

Mus musculus

Synonyms: Lx1, Oct1, Orct, Orct1, Organic cation transporter 1, ...
 
 
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High impact information on Slc22a1

  • Likewise, tissues with large or small average cell sizes contained similar levels of the mRNAs encoding Oct1 or NF-Ya, one of the subunits of the heteromeric CCAAT-binding factor NF-Y, per DNA-equivalent [1].
  • The POU transcription factor Oct-1 represses virus-induced interferon A gene expression [2].
  • Absence of Oct2 in itself had little effect on the pharmacokinetics of tetraethylammonium (TEA), but in Oct1/2(-/-) mice, renal secretion of this compound was completely abolished, leaving only glomerular filtration as a TEA clearance mechanism [3].
  • Their strategic localization in the basolateral membrane of epithelial cells in the liver, intestine (Oct1), and kidney (Oct1 and Oct2) suggests that they play an essential role in removing noxious compounds from the body [3].
  • Since Oct1 and Oct2 have extensively overlapping substrate specificities, they might be functionally redundant [3].
 

Biological context of Slc22a1

 

Anatomical context of Slc22a1

  • Lx1 mRNA is expressed at high levels in mouse liver, kidney, and intestine, and at low levels in the adrenals and in lactating mammary glands [6].
  • Functional expression of mOct1/Slc22a1 in BALB/3T3 cells confers the saturable, temperature-dependent uptake of choline with a K(m) of 42 micrometer, and uptake of TEA with a K(m) of 43 micrometer [8].
  • In conclusion, our data show that Oct1 plays an important role in the uptake of organic cations into the liver and in their direct excretion into the lumen of the small intestine [9].
  • We hypothesize that a multiprotein complex containing GATA-1, Oct-1, and other protein factors may contribute to the formation of a repressive chromatin structure that silences gamma-globin gene expression in normal adult erythrocytes [7].
  • Transfection of rat Oct1 cDNA results in the time-dependent and saturable uptake of metformin by the Chinese hamster ovary cell line with K(m) and V(max) values of 377 microM and 1386 pmol/min/mg of protein, respectively [10].
 

Associations of Slc22a1 with chemical compounds

  • We also demonstrated that organic cation transport by mOct1/Slc22a1 is inhibited by several organic cations, and that the gene is expressed in the perinatal period, at a time when phosphatidylcholine synthesis increases.We conclude that mOct1/Slc22a1 encodes a high affinity mammalian hepatic choline/organic cation transporter [8].
  • The purpose of the present study was to investigate the role of organic cation transporter 1 (Oct1) in the disposition of metformin [10].
 

Other interactions of Slc22a1

  • Uptake of [(3)H]1-methyl-4-phenylpyridinium ([(3)H]MPP(+)) by Xenopus laevis oocytes injected with mOCT1 (Slc22a1) or mOCT2 (Slc22a2) cRNA was attenuated by an increase of extracellular K(+) concentration and under acidic extracellular conditions [11].
  • Slc22a1 expression was increased by PPAR-alpha and -gamma agonist treatment in both murine livers and H35 cells [5].
  • The Lx1 gene maps very close to the imprinted Igf2r/Mpr300 gene on mouse Chromosome (Chr) 17, in a region that is syntenic to human Chr 6q [6].
  • EMSA competition and supershift analyses reveal the formation of multiple DNA-protein complexes at these sites that include Yin Yang 1, Oct1, and NFAT-4 [12].
  • We subsequently used our cell culture uptake system to kinetically define in HepG2 cells a high affinity choline uptake process, which transports choline with a K(m) similar to that of mOct1/Slc22a1 protein [8].

References

  1. Cell size regulation, a mechanism that controls cellular RNA accumulation: consequences on regulation of the ubiquitous transcription factors Oct1 and NF-Y and the liver-enriched transcription factor DBP. Schmidt, E.E., Schibler, U. J. Cell Biol. (1995) [Pubmed]
  2. The POU transcription factor Oct-1 represses virus-induced interferon A gene expression. Mesplède, T., Island, M.L., Christeff, N., Petek, F., Doly, J., Navarro, S. Mol. Cell. Biol. (2005) [Pubmed]
  3. Deficiency in the organic cation transporters 1 and 2 (Oct1/Oct2 [Slc22a1/Slc22a2]) in mice abolishes renal secretion of organic cations. Jonker, J.W., Wagenaar, E., Van Eijl, S., Schinkel, A.H. Mol. Cell. Biol. (2003) [Pubmed]
  4. Cloning and functional expression of a mouse liver organic cation transporter. Green, R.M., Lo, K., Sterritt, C., Beier, D.R. Hepatology (1999) [Pubmed]
  5. Transcriptional regulation of murine Slc22a1 (Oct1) by peroxisome proliferator agonist receptor-alpha and -gamma. Nie, W., Sweetser, S., Rinella, M., Green, R.M. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  6. The Lx1 gene maps to mouse chromosome 17 and codes for a protein that is homologous to glucose and polyspecific transmembrane transporters. Schweifer, N., Barlow, D.P. Mamm. Genome (1996) [Pubmed]
  7. T to C substitution at -175 or -173 of the gamma-globin promoter affects GATA-1 and Oct-1 binding in vitro differently but can independently reproduce the hereditary persistence of fetal hemoglobin phenotype in transgenic mice. Liu, L.R., Du, Z.W., Zhao, H.L., Liu, X.L., Huang, X.D., Shen, J., Ju, L.M., Fang, F.D., Zhang, J.W. J. Biol. Chem. (2005) [Pubmed]
  8. Functional expression of a high affinity mammalian hepatic choline/organic cation transporter. Sinclair, C.J., Chi, K.D., Subramanian, V., Ward, K.L., Green, R.M. J. Lipid Res. (2000) [Pubmed]
  9. Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of the organic cation transporter 1 (Oct1 [Slc22a1]) gene. Jonker, J.W., Wagenaar, E., Mol, C.A., Buitelaar, M., Koepsell, H., Smit, J.W., Schinkel, A.H. Mol. Cell. Biol. (2001) [Pubmed]
  10. Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. Wang, D.S., Jonker, J.W., Kato, Y., Kusuhara, H., Schinkel, A.H., Sugiyama, Y. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  11. Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. Kakehi, M., Koyabu, N., Nakamura, T., Uchiumi, T., Kuwano, M., Ohtani, H., Sawada, Y. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  12. Yin Yang 1, Oct1, and NFAT-4 form repeating, cyclosporin-sensitive regulatory modules within the murine CD21 intronic control region. Zabel, M.D., Wheeler, W., Weis, J.J., Weis, J.H. J. Immunol. (2002) [Pubmed]
 
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