Pregnane X receptor (PXR) regulates P-glycoprotein at the blood-brain barrier: Functional similarities between pig and human PXR

Journal of Pharmacology and Experimental Therapeutics

Volumn 329, Issue 1, 2009, Pages 141-149

  Ott, Melanie ^a   Fricker, Gert ^b   Bauer, Björn ^a,b  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b UNIVERSITY OF MINNESOTA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

16ALPHA CYANOPREGNENOLONE; CALCEIN; GLYCOPROTEIN P; HYPERFORIN; MESSENGER RNA; MULTIDRUG RESISTANCE PROTEIN 1; PREGNANE X RECEPTOR; RIFAMPICIN;

ANIMAL CELL; ARTICLE; BLOOD BRAIN BARRIER; CHEMICAL MODEL; CONTROLLED STUDY; ENDOTHELIUM CELL; GENE EXPRESSION; HUMAN VERSUS ANIMAL COMPARISON; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TRANSPORT; SWINE; TRANSPORT KINETICS; UPREGULATION;

ANIMALS; BICYCLO COMPOUNDS; BLOOD-BRAIN BARRIER; BLOTTING, WESTERN; CELL SEPARATION; CELLS, CULTURED; ENDOTHELIAL CELLS; FLUORESCEINS; HUMANS; IMMUNOHISTOCHEMISTRY; MYOCYTES, SMOOTH MUSCLE; P-GLYCOPROTEIN; PHLOROGLUCINOL; RECEPTORS, STEROID; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RIFAMPIN; RNA, MESSENGER; SWINE; TERPENES; UP-REGULATION; XENOBIOTICS;

EID: 63849146957     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.108.149690     Document Type: Article

References (40)

1. Bauer B, Hartz AM, Fricker G, and Miller DS (2004) Pregnane X receptor up- regulation of P-glycoprotein expression and transport function at the blood-brain barrier. Mol Pharmacol 66:413-419.
2. Bauer B, Hartz AM, Lucking JR, Yang X, Pollack GM, and Miller DS (2008) Coordinated nuclear receptor regulation of the efflux transporter, Mrp2, and the phase-II metabolizing enzyme, GSTpi, at the blood-brain barrier. J Cereb Blood Flow Metab 28:1222-1234.
3. Bauer B, Hartz AM, and Miller DS (2007) Tumor necrosis factor {alpha} and endothelin-1 increase P-glycoprotein expression and transport activity at the blood-brain barrier. Mol Pharmacol 71:667-675.
4. Bauer B, Miller DS, and Fricker G (2003) Compound profiling for P-glycoprotein at the blood-brain barrier using a microplate screening system. Pharm Res 20:1170-1176.
5. Bauer B, Yang X, Hartz AM, Olson ER, Zhao R, Kalvass JC, Pollack GM, and Miller DS (2006) In vivo activation of human PXR tightens the blood-brain barrier to methadone through P-glycoprotein upregulation. Mol Pharmacol 70:1212-1219.
6. Blumberg B, Sabbagh W Jr, Juguilon H, Bolado J Jr, van Meter CM, Ong ES, and Evans RM (1998) SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev 12:3195-3205.
7. Breidenbach T, Hoffmann MW, Becker T, Schlitt H, and Klempnauer J (2000) Drug interaction of St John's wort with cyclosporin. Lancet 355:1912.
8. Bubik M, Ott M, Mahringer A, and Fricker G (2006) Rapid assessment of P-glycoprotein-drug interactions at the blood-brain barrier. Anal Biochem 358:51-58.
9. Cooper BW, Cho TM, Thompson PM, and Wallace AD (2008) Phthalate induction of CYP3A4 is dependent on glucocorticoid regulation of PXR expression. Toxicol Sci 103:268-277.
10. Dussault I and Forman BM (2002) The nuclear receptor PXR: a master regulator of "homeland" defense. Crit Rev Eukaryot Gene Expr 12:53-64.
11. Fellner S, Bauer B, Miller DS, Schaffrik M, Fankhänel M, Spruss T, Bernhardt G, Graeff C, Färber L, Gschaidmeier H, et al. (2002) Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo. J Clin Invest 110:1309-1318.
12. Francis GA, Fayard E, Picard F, and Auwerx J (2003) Nuclear receptors and the control of metabolism. Annu Rev Physiol 65:261-311.
13. Geick A, Eichelbaum M, and Burk O (2001) Nuclear receptor response elements mediate induction ofintestinal MDR1 by rifampin. JBiol Chem 276:14581-14587.
14. Hartz AM, Bauer B, Block ML, Hong JS, and Miller DS (2008) Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P-glycoprotein up-regulation at the blood-brain barrier. FASEB J 22:2723-2733.
15. Haslam IS, Jones K, Coleman T, and Simmons NL (2008) Induction ofP-glycoprotein expression and function in human intestinal epithelial cells (T84). Biochem Pharmacol 76:850-861.
16. Jones SA, Moore LB, Shenk JL, Wisely GB, Hamilton GA, McKee DD, Tomkinson NC, LeCluyse EL, Lambert MH, Willson TM, et al. (2000) The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol 14:27-39.
17. Karliova M, Treichel U, Malagò M, Frilling A, Gerken G, and Broelsch CE (2000) Interaction of Hypericum perforatum (St. John's wort) with cyclosporin A metabolism in a patient after liver transplantation. J Hepatol 33:853-855.
18. Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, Tontonoz P, Kliewer S, Willson TM, and Edwards PA (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.
19. Kawana K, Ikuta T, Kobayashi Y, Gotoh O, Takeda K, and Kawajiri K (2003) Molecular mechanism ofnuclear translocation ofan orphan nuclear receptor, SXR. Mol Pharmacol 63:524-531.
20. Kliewer SA, Goodwin B, and Willson TM (2002) The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism. Endocr Rev 23:687-702.
21. Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, McKee DD, Oliver BB, Willson TM, Zetterstrom RH, et al. (1998) An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92:73-82.
22. Koyano S, Kurose K, Saito Y, Ozawa S, Hasegawa R, Komamura K, Ueno K, Kamakura S, Kitakaze M, Nakajima T, et al. (2004) Functional characterization of four naturally occurring variants of human pregnane X receptor (PXR): one variant causes dramatic loss of both DNA binding activity and the transactivation of the CYP3A4 promoter/enhancer region. Drug Metab Dispos 32:149-154.
23. Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, and Kliewer SA (1998) The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest 102:1016-1023.
24. Löscher W and Potschka H (2005) Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci 6:591-602.
25. Maglich JM, Stoltz CM, Goodwin B, Hawkins-Brown D, Moore JT, and Kliewer SA (2002) Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Mol Pharmacol 62:638-646.
26. Martin P, Riley R, Back DJ, and Owen A (2008) Comparison of the induction profile for drug disposition proteins by typical nuclear receptor activators in human hepatic and intestinal cells. Br J Pharmacol 153:805-819.
27. Moore LB, Goodwin B, Jones SA, Wisely GB, Serabjit-Singh CJ, Willson TM, Collins JL, and Kliewer SA (2000) St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci U S A 97:7500-7502.
28. Moore LB, Maglich JM, McKee DD, Wisely B, Willson TM, Kliewer SA, Lambert MH, and Moore JT (2002) Pregnane X receptor (PXR), constitutive androstane receptor (CAR), and benzoate X receptor (BXR) define three pharmacologically distinct classes of nuclear receptors. Mol Endocrinol 16:977-986.
29. Narang VS, Fraga C, Kumar N, Shen J, Throm S, Stewart CF, and Waters CM (2008) Dexamethasone increases expression and activity of multidrug resistance transporters at the rat blood-brain barrier. Am J Physiol Cell Physiol 295:C440 -450.
30. Orans J, Teotico DG, and Redinbo MR (2005) The nuclear xenobiotic receptor pregnane X receptor: recent insights and new challenges. Mol Endocrinol 19:2891-2900.
31. Pascussi JM, Drocourt L, Fabre JM, Maurel P, and Vilarem MJ (2000) Dexamethasone induces pregnane X receptor and retinoid X receptor-alpha expression in human hepatocytes: synergistic increase of CYP3A4 induction by pregnane X receptor activators. Mol Pharmacol 58:361-372.
32. Perloff MD, von Moltke LL, Fahey JM, and Greenblatt DJ (2007) Induction of P-glycoprotein expression and activity by ritonavir in bovine brain microvessel endothelial cells. J Pharm Pharmacol 59:947-953.
33. Pfaffl MW, Horgan GW, and Dempfle L (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30:e36.
34. Rosenfeld JM, Vargas R Jr, Xie W, and Evans RM (2003) Genetic profiling defines the xenobiotic gene network controlled by the nuclear receptor pregnane X receptor. Mol Endocrinol 17:1268-1282.
35. Ruschitzka F, Meier PJ, Turina M, Lüscher TF, and Noll G (2000) Acute heart transplant rejection due to Saint John's wort. Lancet 355:548-549.
36. Schinkel AH (1999) P-Glycoprotein, a gatekeeper in the blood-brain barrier. Adv Drug Deliv Rev 36:179-194.
37. Schinkel AH, Smit JJ, van Tellingen O, Beijnen JH, Wagenaar E, van Deemter L, Mol CA, van der Valk MA, Robanus-Maandag EC, and te Riele HP (1994) Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 77:491-502.
38. Squires EJ, Sueyoshi T, and Negishi M (2004) Cytoplasmic localization of pregnane X receptor and ligand-dependent nuclear translocation in mouse liver. J Biol Chem 279:49307-49314.
39. Synold TW, Dussault I, and Forman BM (2001) The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med 7:584-590.
40. Wang H and LeCluyse EL (2003) Role of orphan nuclear receptors in the regulation of drug-metabolising enzymes. Clin Pharmacokinet 42:1331-1357.