916
Views
64
CrossRef citations to date
0
Altmetric
Review Article

Nuclear-receptor–mediated regulation of drug– and bile-acid–transporter proteins in gut and liver

, , &
Pages 48-59 | Received 30 Aug 2012, Accepted 07 Nov 2012, Published online: 21 Jan 2013

References

  • Aiba, T., Susa, M., Fukumori, S., Hashimoto, Y. (2005). The effects of culture conditions on CYP3A4 and MDR1 mRNA induction by 1alpha,25-dihydroxyvitamin D(3) in human intestinal cell lines, Caco-2 and LS180. Drug Metab Pharmacokinet 20:268–274.
  • Aleksunes, L. M., Klaassen, C. D. (2012). Coordinated regulation of hepatic phase I and II drug-metabolizing genes and transporters using AhR-, CAR-, PXR-, PPARalpha-, and Nrf2-null mice. Drug Metab Dispos 40:1366–1379.
  • Allen, J. D., Schinkel, A. H. (2002). Multidrug resistance and pharmacological protection mediated by the breast cancer resistance protein (BCRP/ABCG2). Mol Cancer Ther 1:427–434.
  • Ananthanarayanan, M., Balasubramanian, N., Makishima, M., Mangelsdorf, D. J., Suchy, F. J. (2001). Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. J Biol Chem 276:28857–28865.
  • Assem, M., Schuetz, E. G., Leggas, M., Sun, D., Yasuda, K., Reid, G., et al. (2004). Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice. J Biol Chem 279:22250–22257.
  • Ballatori, N., Christian, W. V., Lee, J. Y., Dawson, P. A., Soroka, C. J., Boyer, J. L., et al. (2005). OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia. Hepatology 42:1270–1279.
  • Burk, O., Arnold, K. A., Geic.k, A., Tegude, H., Eichelbaum, M. (2005). A role for constitutive androstane receptor in the regulation of human intestinal MDR1 expression. Biol Chem 386:503–513.
  • Cascorbi, I. (2011). P-glycoprotein: tissue distribution, substrates, and functional consequences of genetic variations. Handb Exp Pharmacol 261–283.
  • Chai, J., Luo, D., Wu, X., Wang, H., He, Y., Li, Q., et al. (2011). Changes of organic anion transporter MRP4 and related nuclear receptors in human obstructive cholestasis. J Gastrointest Surg 15:996–1004.
  • Cheng, X., Klaassen, C. D. (2006). Regulation of mRNA expression of xenobiotic transporters by the pregnane x receptor in mouse liver, kidney, and intestine. Drug Metab Dispos 34:1863–1867.
  • Chow, E. C., Maeng, H. J., Liu, S., Khan, A. A., Groothuis, G. M., PANG, K. S. (2009). 1alpha,25-Dihydroxyvitamin D(3) triggered vitamin D receptor and farnesoid X receptor-like effects in rat intestine and liver in vivo. Biopharm Drug Dispos 30:457–475.
  • Chow, E. C., Sun, H., Khan, A. A., Groothuis, G. M., Pang, K. S. (2010). Effects of 1alpha,25-dihydroxyvitamin D3 on transporters and enzymes of the rat intestine and kidney in vivo. Biopharm Drug Dispos 31:91–108.
  • Dawson, P. A. (2011). Role of the intestinal bile acid transporters in bile acid and drug disposition. Handb Exp Pharmacol 169–203.
  • Dawson, P. A., Hubbert, M., Haywood, J., Craddock, A. L., Zerangue, N., Christian, W. V., et al. (2005). The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta, is an ileal basolateral bile acid transporter. J Biol Chem 280:6960–6968.
  • Denson, L. A., Sturm, E., Echevarria, W., Zimmerman, T. L., Makishima, M., Mangelsdorf, D. J., et al. (2001). The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp. Gastroenterology 121:140–147.
  • Doyle, L. A., Ross, D. D. (2003). Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene 22:7340–7358.
  • Dueland, S., Reichen, J., Everson, G. T., Davis, R. A. (1991). Regulation of cholesterol and bile acid homoeostasis in bile-obstructed rats. Biochem J 280 (Pt 2):373–377.
  • Eloranta, J. J., Hiller, C., Juttner, M., Kullak-Ublick, G. A. (2012). The SLCO1A2 gene, encoding human organic anion-transporting polypeptide 1A2, is transactivated by the vitamin D receptor. Mol Pharmacol 82:37–46.
  • Gahir, S. S., Piquette-Miller, M. (2011). Gestational and pregnane X receptor-mediated regulation of placental ATP-binding cassette drug transporters in mice. Drug Metab Dispos 39:465–471.
  • Gartung, C., Ananthanarayanan, M., Rahman, M. A., Schuele, S., Nundy, S., Soroka, C. J., et al. (1996). Down-regulation of expression and function of the rat liver Na+/bile acid cotransporter in extrahepatic cholestasis. Gastroenterology 110:199–209.
  • Geick, A., Eichelbaum, M., Burk, O. (2001). Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem 276:14581–14587.
  • Glaeser, H., Bailey, D. G., Dresser, G. K., Gregor, J. C., Schwarz, U. I., McGrath, J. S., et al. (2007). Intestinal drug transporter expression and the impact of grapefruit juice in humans. Clin Pharmacol Ther 81:362–370.
  • Goodwin, B., Jones, S. A., Price, R. R., Watson, M. A., McKee, D. D., Moore, L. B., et al. (2000). A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell 6:517–526.
  • Greiner, B., Eichelbaum, M., Fritz, P., Kreichgauer, H. P., von Richter, O., Zundler, J., et al. (1999). The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J Clin Invest 104:147–153.
  • Gui, C., Miao, Y., Thompson, L., Wahlgren, B., Mock, M., Stieger, B., et al. (2008). Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. Eur J Pharmacol 584:57–65.
  • Guo, G. L., Lambert, G., Negishi, M., Ward, J. M., Brewer, H. B., Jr., Kliewer, S. A., et al. (2003). Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity. J Biol Chem 278:45062–45071.
  • Gustafsson, J. (1978). Effect of biliary obstruction on 26-hydroxylation of C27-steroids in bile acid synthesis. J Lipid Res 19:237–243.
  • Hagenbuch, B., Dawson, P. (2004). The sodium bile salt cotransport family SLC10. Pflugers Arch 447:566–570.
  • Hagenbuch, B., Meier, P. J. (2004). Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers Arch 447:653–665.
  • Hirano, M., Maeda, K., Shitara, Y., Sugiyama, Y. (2004). Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the hepatic uptake of pitavastatin in humans. J Pharmacol Exp Ther 311:139–146.
  • Ho, R. H., Tirona, R. G., Leake, B. F., Glaeser, H., Lee, W., Lemke, C. J., WANG, Y. KIM, R. B. 2006. Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology 130:1793–1806.
  • Honda, A., Ikegami, T., Nakamuta, M., Miyazaki, T., Iwamoto, J., Hirayama, T., et al. (2012). Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid. Hepatology Aug 22. doi: 10.1002/hep.26018. [Epub ahead of print].
  • Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., et al. (2005). Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab 2:217–225.
  • Jiang, H., Chen, K., He, J., Pan, F., Li, J., Chen, J., et al. (2009). Association of pregnane X receptor with multidrug resistance-related protein 3 and its role in human colon cancer chemoresistance. J Gastrointest Surg 13:1831–1838.
  • Jigorel, E., Le Vee, M., Boursier-Neyret, C., Parmentier, Y., Fardel, O. (2006). Differential regulation of sinusoidal and canalicular hepatic drug transporter expression by xenobiotics activating drug-sensing receptors in primary human hepatocytes. Drug Metab Dispos 34:1756–1763.
  • Jung, D., Fried, M., Kullak-Ublick, G. A. (2002a). Human apical sodium-dependent bile salt transporter gene (SLC10A2) is regulated by the peroxisome proliferator-activated receptor alpha. J Biol Chem 277:30559–30566.
  • Jung, D., Podvinec, M., Meyer, U. A., Mangelsdorf, D. J., Fried, M., Meier, P. J., et al. (2002b). Human organic anion transporting polypeptide 8 promoter is transactivated by the farnesoid X receptor/bile acid receptor. Gastroenterology 122:1954–1966.
  • Juranka, P. F., Zastawny, R. L., Ling, V. (1989). P-glycoprotein: multidrug-resistance and a superfamily of membrane-associated transport proteins. FASEB J 3:2583–2592.
  • Kast, H. R., Goodwin, B., Tarr, P. T., Jones, S. A., Anisfeld, A. M., Stoltz, C. M., et al. (2002). Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem 277:2908–2915.
  • Keppler, D. (2011). Multidrug resistance proteins (MRPs, ABCCs): importance for pathophysiology and drug therapy. Handb Exp Pharmacol 299–323.
  • Khan, A. A., Chow, E. C., Porte, R. J., Pang, K. S., Groothuis, G. M. (2009). Expression and regulation of the bile acid transporter, OSTalpha-OSTbeta in rat and human intestine and liver. Biopharm Drug Dispos 30:241–258.
  • Khan, A. A., Chow, E. C., Porte, R. J., Pang, K. S., Groothuis, G. M. (2011). The role of lithocholic acid in the regulation of bile acid detoxication, synthesis, and transport proteins in rat and human intestine and liver slices. Toxicol In Vitro 25:80–90.
  • Klaassen, C. D., Aleksunes, L. M. (2010). Xenobiotic, bile acid, and cholesterol transporters: function and regulation. Pharmacol Rev 62:1–96.
  • Klaassen, C. D., Lu, H. (2008). Xenobiotic transporters: ascribing function from gene knockout and mutation studies. Toxicol Sci 101:186–196.
  • Kurata, Y., Ieiri, I., Kimura, M., Morita, T., Irie, S., Urae, A., et al. (2002). Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein. Clin Pharmacol Ther 72:209–219.
  • Landrier, J. F., Eloranta, J. J., Vavricka, S. R., Kullak-Ublick, G. A. (2006). The nuclear receptor for bile acids, FXR, transactivates human organic solute transporter-alpha and -beta genes. Am J Physiol Gastrointest Liver Physiol 290:G476–G485.
  • Lu, T. T., Makishima, M., Repa, J. J., Schoonjans, K., Kerr, T. A., Auwerx, J., et al. (2000). Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell 6:507–515.
  • Meijerman, I., Beijnen, J. H., Schellens, J. H. (2008). Combined action and regulation of phase II enzymes and multidrug resistance proteins in multidrug resistance in cancer. Cancer Treat Rev 34:505–520.
  • Meyer zu Schwabedissen, H. E., Bottcher, K., Chaudhry, A., Kroemer, H. K., Schuetz, E. G., Kim, R. B. (2010). Liver X receptor alpha and farnesoid X receptor are major transcriptional regulators of OATP1B1. Hepatology 52:1797–1807.
  • Meyer zu Schwabedissen, H. E., Kim, R. B. (2009). Hepatic OATP1B transporters and nuclear receptors PXR and CAR: interplay, regulation of drug disposition genes, and single nucleotide polymorphisms. Mol Pharm 6:1644–1661.
  • Meyer zu Schwabedissen, H. E., Tirona, R. G., Yip, C. S., Ho, R. H., Kim, R. B. (2008). Interplay between the nuclear receptor pregnane X receptor and the uptake transporter organic anion transporter polypeptide 1A2 selectively enhances estrogen effects in breast cancer. Cancer Res 68:9338–9347.
  • Miki, Y., Suzuki, T., Kitada, K., Yabuki, N., Shibuya, R., Moriya, T., et al. (2006). Expression of the steroid and xenobiotic receptor and its possible target gene, organic anion transporting polypeptide-A, in human breast carcinoma. Cancer Res 66:535–542.
  • Moreau, A., Maurel, P., Vilarem, M. J., Pascussi, J. M. (2007). Constitutive androstane receptor-vitamin D receptor crosstalk: consequence on CYP24 gene expression. Biochem Biophys Res Commun 360:76–82.
  • Nagano, M., Kuroki, S., Mizuta, A., Furukawa, M., Noshiro, M., Chijiiwa, K., et al. (2004). Regulation of bile acid synthesis under reconstructed enterohepatic circulation in rats. Steroids 69:701–709.
  • Neimark, E., Chen, F., Li, X., Shneider, B. L. (2004). Bile acid-induced negative feedback regulation of the human ileal bile acid transporter. Hepatology 40:149–156.
  • Oelkers, P., Kirby, L. C., Heubi, J. E., Dawson, P. A. (1997). Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). J Clin Invest 99:1880–1887.
  • Olinga, P., Elferink, M. G., Draaisma, A. L., Merema, M. T., Castell, J. V., Perez, G., et al. (2008). Coordinated induction of drug transporters and phase I and II metabolism in human liver slices. Eur J Pharm Sci 33:380–389.
  • Oscarson, M., Zanger, U. M., Rifki, O. F., Klein, K., Eichelbaum, M., Meyer, U. A. (2006). Transcriptional profiling of genes induced in the livers of patients treated with carbamazepine. Clin Pharmacol Ther 80:440–456.
  • Ourlin, J. C., Lasserre, F., Pineau, T., Fabre, J. M., Sa-Cunha, A., Maurel, P., et al. (2003). The small heterodimer partner interacts with the pregnane X receptor and represses its transcriptional activity. Mol Endocrinol 17:1693–1703.
  • Pandak, W. M., Li, Y. C., Chiang, J. Y., Studer, E. J., Gurley, E. C., Heuman, D. M., et al. (1991). Regulation of cholesterol 7 alpha-hydroxylase mRNA and transcriptional activity by taurocholate and cholesterol in the chronic biliary diverted rat. J Biol Chem 266:3416–3421.
  • Pascussi, J. M., Robert, A., Nguyen, M., Walrant-Debray, O., Garabedian, M., Martin, P., et al. (2005). Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest 115:177–186.
  • Potthoff, M. J., Kliewer, S. A., Mangelsdorf, D. J. (2012). Endocrine fibroblast growth factors 15/19 and 21: from feast to famine. Genes Dev 26:312–324.
  • Renga, B., Migliorati, M., Mencarelli, A., Cipriani, S., D’Amore, C., Distrutti, E., et al. (2011). Farnesoid X receptor suppresses constitutive androstane receptor activity at the multidrug resistance protein-4 promoter. Biochim Biophys Acta 1809:157–165.
  • Roglans, N., Sanguino, E., Peris, C., Alegret, M., Vazquez, M., Adzet, T., DIAZ, C., et al. (2002). Atorvastatin treatment induced peroxisome proliferator-activated receptor alpha expression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats. J Pharmacol Exp Ther 302:232–239.
  • Saeki, M., Kurose, K., Tohkin, M., Hasegawa, R. (2008). Identification of the functional vitamin D response elements in the human MDR1 gene. Biochem Pharmacol 76:531–542.
  • Schmiedlin-Ren, P., Thummel, K. E., Fisher, J. M., Paine, M. F., Lown, K. S., Watkins, P. B. (1997). Expression of enzymatically active CYP3A4 by Caco-2 cells grown on extracellular matrix-coated permeable supports in the presence of 1alpha,25-dihydroxyvitamin D3. Mol Pharmacol 51:741–754.
  • Schroeder, A., Eckhardt, U., Stieger, B., Tynes, R., Schteingart, C. D., Hofmann, A. F., et al. (1998). Substrate specificity of the rat liver Na(+)-bile salt cotransporter in Xenopus laevis oocytes and in CHO cells. Am J Physiol 274:G370–G375.
  • Schuetz, E. G., Beck, W. T., Schuetz, J. D. (1996). Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol 49:311–318.
  • Schuetz, E. G., Strom, S., Yasuda, K., Lecureur, V., Assem, M., Brimer, C., et al. (2001). Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear hormone receptors, transporters, and cytochrome P450. J Biol Chem 276:39411–39418.
  • Siegmund, W., Altmannsberger, S., Paneitz, A., Hecker, U., Zschiesche, M., Franke, G., et al. (2002a). Effect of levothyroxine administration on intestinal P-glycoprotein expression: consequences for drug disposition. Clin Pharmacol Ther 72:256–264.
  • Siegmund, W., Ludwig, K., Giessmann, T., Dazert, P., Schroeder, E., Sperker, B., et al. (2002b). The effects of the human MDR1 genotype on the expression of duodenal P-glycoprotein and disposition of the probe drug talinolol. Clin Pharmacol Ther 72:572–583.
  • Smetanina, M. A., Pakharukova, M. Y., Kurinna, S. M., Dong, B., Hernandez, J. P., Moore, D. D., et al. (2011). Ortho-aminoazotoluene activates mouse constitutive androstane receptor (mCAR) and increases expression of mCAR target genes. Toxicol Appl Pharmacol 255:76–85.
  • Song, X., Kaimal, R., Yan, B., Deng, R. (2008). Liver receptor homolog 1 transcriptionally regulates human bile salt export pump expression. J Lipid Res 49:973–984.
  • Staudinger, J. L., Madan, A., Carol, K. M., Parkinson, A. (2003). Regulation of drug transporter gene expression by nuclear receptors. Drug Metab Dispos 31:523–527.
  • Tamasi, V., Juvan, P., Beer, M., Rozman, D., Meyer, U. A. (2009). Transcriptional activation of PPARalpha by phenobarbital in the absence of CAR and PXR. Mol Pharm 6:1573–1581.
  • Tirona, R. G. (2011). Molecular mechanisms of drug transporter regulation. Handb Exp Pharmacol 373–402.
  • Tirona, R. G., Leake, B. F., Wolkoff, A. W., Kim, R. B. (2003). Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther 304:223–228.
  • van de Steeg, E., Stránecký, V., Hartmannová, H., Nosková, L., Hřebíček, M., Wagenaar, E., et al. (2012). Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J Clin Invest 122:519–528.
  • Wagner, M., Halilbasic, E., Marschall, H. U., Zollner, G., Fickert, P., Langner, C., et al. (2005). CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice. Hepatology 42:420–430.
  • Wang, L., Lee, Y. K., Bundman, D., Han, Y., Thevananther, S., Kim, C. S., et al. (2002). Redundant pathways for negative feedback regulation of bile acid production. Dev Cell 2:721–731.
  • Wilkinson, G. R. (2005). Drug metabolism and variability among patients in drug response. New Engl J Med 352:2211–2221.
  • Wong, M. H., Oelkers, P., Dawson, P. A. (1995). Identification of a mutation in the ileal sodium-dependent bile acid transporter gene that abolishes transport activity. J Biol Chem 270:27228–27234.
  • Yanni, S. B., Augustijns, P. F., Benjamin, D. K., Jr., Brouwer, K. L., Thakker, D. R., Annaert, P. P. (2010). In vitro investigation of the hepatobiliary disposition mechanisms of the antifungal agent micafungin in humans and rats. Drug Metab Dispos 38:1848–1856.
  • Zhang, C., Kwan, P., Zuo, Z., Baum, L. (2012). The transport of antiepileptic drugs by P-glycoprotein. Adv Drug Deliv Rev 64:930–942.
  • Zollner, G., Fickert, P., Fuchsbichler, A., Silbert, D., Wagner, M., Arbeiter, S., et al. (2003). Role of nuclear bile acid receptor, FXR, in adaptive ABC transporter regulation by cholic and ursodeoxycholic acid in mouse liver, kidney, and intestine. J Hepatol 39:480–488.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.