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Gene Review

Slc10a1  -  solute carrier family 10 (sodium/bile acid...

Mus musculus

Synonyms: Na(+)/bile acid cotransporter, Na(+)/taurocholate transport protein, Ntcp, Sodium/bile acid cotransporter, Sodium/taurocholate cotransporting polypeptide, ...
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Disease relevance of Slc10a1


High impact information on Slc10a1


Biological context of Slc10a1

  • The down-regulation of Ntcp1 (Slc10a1) protein expression might protect hepatocytes from high intracellular bile-salt loads [8].
  • To isolate the murine Na+/taurocholate cotransporting polypeptide (Ntcp), we screened a mouse liver cDNA library and identified Ntcp1, encoding a 362 amino acid protein and Ntcp2, encoding a 317 amino acid protein which had a shorter C-terminal end [9].

Anatomical context of Slc10a1

  • Ntcp protein levels were 4-6-fold reduced in plasma membranes of (-/-) mice relative to sex-matched controls [1].
  • A weak cytostatic effect of BANB-1, BANB-2 and BANB-3 was detected even in CHO cells stably transfected with rat bile acid transporters (Ntcp and Oatp1/1a1) [10].
  • To study the time course for the changes in serum bile acid levels as well as SHP-1 and Ntcp steady-state mRNA levels, mice were subjected to common bile duct ligation (CBDL) for 3, 6, 12, 24, 72, and 168 h and compared with sham-operated controls [11].

Associations of Slc10a1 with chemical compounds

  • The bile salt uptake system Na(+)-taurocholate co-transporting polypeptide (Ntcp) and organic anion transporting polypeptide-1 (Oatp1) were down-regulated by taurocholate and not affected by cholestyramine feeding [12].
  • Bile acid-induced, farnesoid X receptor (FXR)-mediated induction of the nuclear repressor short heterodimer partner (SHP) has been proposed as a key mechanism reducing Ntcp expression [13].
  • All cysteines of mouse ileal and hepatic sodium-dependent bile acid transporters (Isbt and Ntcp, respectively) were individually replaced by alanine [14].
  • Ntcp levels were preserved in APAP-exposed livers and reduced to 30-50% of control after CCl4 [2].

Other interactions of Slc10a1

  • CONCLUSIONS: Large variations in hepatic bile salt flux have minor effects on expression of murine Ntcp and Bsep in vivo, suggesting that these transporters are abundantly expressed and able to accommodate a wide range of 'physiological' bile salt fluxes [12].
  • Cyp7A(-/-) mice did not show altered Ntcp or Oatp1 expression [12].
  • However, the role of FXR and SHP or other nuclear receptors and hepatocyte-enriched transcription factors in mediating Ntcp repression in obstructive cholestasis is unclear [13].
  • CONCLUSIONS: Elevated plasma bile salt levels in mdr2 P-glycoprotein-deficient mice in the absence of overt cholestasis are associated with reduced Ntcp expression and transport activity [1].
  • Of these, the ileal sodium bile acid transporter (isbt) and the hepatic sodium bile acid cotransporting polypeptide (ntcp) may be most important in determining the efficiency of bile acid recovery within the enterohepatic circulation [15].

Analytical, diagnostic and therapeutic context of Slc10a1


  1. Decreased Na+-dependent taurocholate uptake and low expression of the sinusoidal Na+-taurocholate cotransporting protein (Ntcp) in livers of mdr2 P-glycoprotein-deficient mice. Koopen, N.R., Wolters, H., Voshol, P., Stieger, B., Vonk, R.J., Meier, P.J., Kuipers, F., Hagenbuch, B. J. Hepatol. (1999) [Pubmed]
  2. Coordinated expression of multidrug resistance-associated proteins (Mrps) in mouse liver during toxicant-induced injury. Aleksunes, L.M., Scheffer, G.L., Jakowski, A.B., Pruimboom-Brees, I.M., Manautou, J.E. Toxicol. Sci. (2006) [Pubmed]
  3. Hepatocyte nuclear factor-1alpha is an essential regulator of bile acid and plasma cholesterol metabolism. Shih, D.Q., Bussen, M., Sehayek, E., Ananthanarayanan, M., Shneider, B.L., Suchy, F.J., Shefer, S., Bollileni, J.S., Gonzalez, F.J., Breslow, J.L., Stoffel, M. Nat. Genet. (2001) [Pubmed]
  4. Elevated levels of hepatocyte nuclear factor 3beta in mouse hepatocytes influence expression of genes involved in bile acid and glucose homeostasis. Rausa, F.M., Tan, Y., Zhou, H., Yoo, K.W., Stolz, D.B., Watkins, S.C., Franks, R.R., Unterman, T.G., Costa, R.H. Mol. Cell. Biol. (2000) [Pubmed]
  5. Hepatic overexpression of caveolins increases bile salt secretion in mice. Moreno, M., Molina, H., Amigo, L., Zanlungo, S., Arrese, M., Rigotti, A., Miquel, J.F. Hepatology (2003) [Pubmed]
  6. Targeted deletion of the ileal bile acid transporter eliminates enterohepatic cycling of bile acids in mice. Dawson, P.A., Haywood, J., Craddock, A.L., Wilson, M., Tietjen, M., Kluckman, K., Maeda, N., Parks, J.S. J. Biol. Chem. (2003) [Pubmed]
  7. Protective role of hydroxysteroid sulfotransferase in lithocholic acid-induced liver toxicity. Kitada, H., Miyata, M., Nakamura, T., Tozawa, A., Honma, W., Shimada, M., Nagata, K., Sinal, C.J., Guo, G.L., Gonzalez, F.J., Yamazoe, Y. J. Biol. Chem. (2003) [Pubmed]
  8. Expression of liver plasma membrane transporters in gallstone-susceptible and gallstone-resistant mice. Müller, O., Schalla, C., Scheibner, J., Stange, E.F., Fuchs, M. Biochem. J. (2002) [Pubmed]
  9. Molecular cloning and functional characterization of two alternatively spliced Ntcp isoforms from mouse liver1. Cattori, V., Eckhardt, U., Hagenbuch, B. Biochim. Biophys. Acta (1999) [Pubmed]
  10. Novel bile acid derivatives (BANBs) with cytostatic activity obtained by conjugation of their side chain with nitrogenated bases. Vallejo, M., Castro, M.A., Medarde, M., Macias, R.I., Romero, M.R., El-Mir, M.Y., Monte, M.J., Briz, O., Serrano, M.A., Marin, J.J. Biochem. Pharmacol. (2007) [Pubmed]
  11. Induction of short heterodimer partner 1 precedes downregulation of Ntcp in bile duct-ligated mice. Zollner, G., Fickert, P., Silbert, D., Fuchsbichler, A., Stumptner, C., Zatloukal, K., Denk, H., Trauner, M. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  12. Effects of bile salt flux variations on the expression of hepatic bile salt transporters in vivo in mice. Wolters, H., Elzinga, B.M., Baller, J.F., Boverhof, R., Schwarz, M., Stieger, B., Verkade, H.J., Kuipers, F. J. Hepatol. (2002) [Pubmed]
  13. Role of nuclear receptors and hepatocyte-enriched transcription factors for Ntcp repression in biliary obstruction in mouse liver. Zollner, G., Wagner, M., Fickert, P., Geier, A., Fuchsbichler, A., Silbert, D., Gumhold, J., Zatloukal, K., Kaser, A., Tilg, H., Denk, H., Trauner, M. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  14. Effects of Cys mutation on taurocholic acid transport by mouse ileal and hepatic sodium-dependent bile acid transporters. Saeki, T., Kuroda, T., Matsumoto, M., Kanamoto, R., Iwami, K. Biosci. Biotechnol. Biochem. (2002) [Pubmed]
  15. Coordinate regulation of bile acid biosynthetic and recovery pathways. Torchia, E.C., Cheema, S.K., Agellon, L.B. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  16. Liver disease with altered bile acid transport in Niemann-Pick C mice on a high-fat, 1% cholesterol diet. Erickson, R.P., Bhattacharyya, A., Hunter, R.J., Heidenreich, R.A., Cherrington, N.J. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
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