Pregnane X Receptor and P-glycoprotein: A connexion for Alzheimer’s disease management

Molecular Diversity

Volumn 18, Issue 4, 2014, Pages 895-909

  Jain, Sumit ^a   Rathod, Vijay ^a   Prajapati, Rameshwar ^a   Nandekar, Prajwal P ^a   Sangamwar, Abhay T ^a  

^a NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH NIPER   (India)

Author keywords

Alzheimer s disease; Amyloid beta (A ); Blood brain barrier (BBB); In silico; Neuroinflammation; P glycoprotein (Pgp); Pregnane X Receptor (PXR)

Indexed keywords

4,4' ISOPROPYLIDENEDIPHENOL; ABC TRANSPORTER A1; AMPRENAVIR; CAMPTOTHECIN; CARBAMAZEPINE; CERIVASTATIN; CLINDAMYCIN; CLOTRIMAZOLE; CORTICOSTERONE; DEXAMETHASONE; DICLOXACILLIN; DOCETAXEL; FARNESOID X RECEPTOR; FARNOQUINONE; FENVALERATE; FLUCONAZOLE; FUCOXANTHIN; ITRACONAZOLE; MEVINOLIN; MULTIDRUG RESISTANCE PROTEIN; PACLITAXEL; PHENOBARBITAL; PREGNANE X RECEPTOR; RIFAMPICIN; SESAMIN; STIGMASTEROL; UNINDEXED DRUG; VERAPAMIL; VINCRISTINE; ABC TRANSPORTER; PROTEIN BINDING; STEROID RECEPTOR;

ALZHEIMER DISEASE; ARTICLE; BLOOD BRAIN BARRIER; CENTRAL NERVOUS SYSTEM; COMPUTER MODEL; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; DRUG BINDING; HUMAN; IN VITRO STUDY; NERVOUS SYSTEM INFLAMMATION; NEUROFIBRILLARY TANGLE; OLIGODENDROGLIA; PATHOPHYSIOLOGY; STAPHYLOCOCCUS AUREUS; UPREGULATION; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; DISEASE MANAGEMENT; GENETICS; INFLAMMATION; METABOLISM; MOLECULARLY TARGETED THERAPY; PROTEIN CONFORMATION;

ALZHEIMER DISEASE; ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; DISEASE MANAGEMENT; HUMANS; INFLAMMATION; MODELS, MOLECULAR; MOLECULAR TARGETED THERAPY; P-GLYCOPROTEIN; PROTEIN BINDING; PROTEIN CONFORMATION; RECEPTORS, STEROID;

EID: 84909988832     PISSN: 13811991     EISSN: 1573501X     Source Type: Journal    
DOI: 10.1007/s11030-014-9550-6     Document Type: Article

References (131)

1. Graeber MB, Mehraein P (1999) Reanalysis of the first case of Alzheimers disease. Eur Arch Psychiatry Clin Neurosci 249:S10–S13. doi:10.1007/PL00014167
2. Thies W, Bleiler L, Alzheimer’s Association (2013) 2013 Alzheimer’s disease facts and figures. Alzheimers Dement 9:208–245. doi:10.1016/j.jalz.2013.02.003
3. Detailed Tables for the National Vital Statistics Report. Deaths: Final Data for 2010. National Center for Health Statistics. http://www.cdc.gov/nchs/data/dvs/deaths2010release.pdf
4. Aprahamian I, Stella F, Forlenza OV (2013) New treatment strategies for Alzheimer’s disease: Is there a hope? Indian J Med Res 138:449–460
5. Geerts H, Roberts P, Spiros A, Carr R (2013) A strategy for developing new treatment paradigms for neuropsychiatric and neurocognitive symptoms in Alzheimers disease. Front Pharmacol 4:1–10. doi:10.3389/fphar.2013.00047
6. Kliewer SA, Goodwin B, Willson TM (2002) The nuclear pregnane X receptor: A key regulator of xenobiotic metabolism. Endocr Rev 23:687–702. doi:10.1210/er.2001-0038
7. Hartz AMS, Miller DS, Bauer B (2010) Restoring blood–brain barrier P-glycoprotein reduces brain amyloid-$$\beta $$β in a mouse model of Alzheimer’s disease. Mol Pharmacol 77:715–723. doi: 10.1124/mol.109.061754
8. Schumacher U, Mollgard K (1997) The multidrug-resistance P-glycoprotein (Pgp, MDR1) is an early marker of blood–brain barrier development in the microvessels of the developing human brain. Histochem Cell Biol 108:179–182. doi:10.1007/s004180050159
9. Braak H, Braak E (1997) Diagnostic criteria for neuropathologic assessment of Alzheimers disease. Neurobiol Aging 18:85–88. doi:10.1016/S0197-4580(97)00062-6
10. Kazee AM, Johnson EM (1998) Alzheimer’s disease pathology in non-demented elderly. J Alzheimers Dis 1:81–89
11. Selkoe DJ, Wolfe MS (2007) Presenilin: Running with scissors in the membrane. Cell 131:215–221. doi:10.1016/j.cell.2007.10.012
12. D’Andrea MR, Nagele RG, Wang H-Y, Lee DHS (2002) Consistent immunohistochemical detection of intracellular $$\beta $$β-amyloid42 in pyramidal neurons of Alzheimer’s disease entorhinal cortex. Neurosci Lett 333:163–166. doi: 10.1016/S0304-3940(02)00875-3
13. Arnold SE, Hyman BT, Flory J, Damasio AR, Van Hoesen GW (1991) The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer’s disease. Cereb Cortex 1:103–116. doi:10.1093/cercor/1.1.103
14. Kukar T, Murphy MP, Eriksen JL, Sagi SA, Weggen S, Smith TE, Ladd T, Khan MA, Kache R, Beard J (2005) Diverse compounds mimic Alzheimer disease causing mutations by augmenting A$$\beta $$β42 production. Nat Med 11:545–550. doi: 10.1038/nm1235
15. Hecimovic S, Wang J, Dolios G, Martinez M, Wang R, Goate AM (2004) Mutations in APP have independent effects on A$$\beta $$β and CTF$$\gamma $$γ generation. Neurobiol Dis 17:205–218. doi: 10.1016/j.nbd.2004.04.018
16. Wakutani Y, Watanabe K, Adachi Y, Wada-Isoe K, Urakami K, Ninomiya H, Saido TC, Hashimoto T, Iwatsubo T, Nakashima K (2004) Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimers disease. J Neurol Neurosurg Psychiatry 75:1039–1042. doi:10.1136/jnnp.2003.010611
17. Itagaki S, McGeer PL, Akiyama H, Zhu S, Selkoe D (1989) Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease. J Neuroimmunol 24:173–182. doi:10.1016/0165-5728(89)90115-X
18. Meda L, Cassatella MA, Szendrei GI, Otvos L, Baron P, Villalba M, Ferrari D, Rossi F (1995) Activation of microglial cells by $$\beta $$β-amyloid protein and interferon-$$\gamma $$γ. Nature 374:647–650. doi: 10.1038/374647a0
19. di Masi A, Marinis ED, Ascenzi P, Marino M (2009) Nuclear receptors CAR and PXR: Molecular, functional, and biomedical aspects. Mol Asp Med 30:297–343. doi:10.1016/j.mam.2009.04.002
20. Rathod V, Jain S, Nandekar P, Sangamwar AT (2014) Human pregnane X receptor: A novel target for anticancer drug development. Drug Discov Today 19:63–70. doi:10.1016/j.drudis.2013.08.009
21. Moore LB, Maglich JM, McKee DD, Wisely B, Willson TM, Kliewer SA, Lambert MH, 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
22. Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, McKee DD, Oliver BB, Willson TM (1998) An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92:73–82. doi:10.1016/S0092-8674(00)80900-9
23. Kliewer SA, Goodwin B, Willson TM (2002) The nuclear pregnane X receptor: A key regulator of xenobiotic metabolism. Endocr Rev 23:687–702. doi:10.1210/er.2001-0038
24. Pondugula SR, Mani S (2013) Pregnane xenobiotic receptor in cancer pathogenesis and therapeutic response. Cancer Lett 328:1–9. doi:10.1016/j.canlet.2012.08.030
25. Begley DJ (2004) ABC transporters and the blood–brain barrier. Curr Pharm Des 10:1295–1312. doi:10.2174/1381612043384844
26. Sun H, Dai H, Shaik N, Elmquist WF (2003) Drug efflux transporters in the CNS. Adv Drug Deliv Rev 55:83–105. doi:10.1016/S0169-409X(02)00172-2
27. Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ (2010) Structure and function of the blood brain barrier. Neurobiol Dis 37:13–25. doi:10.1016/j.nbd.2009.07.030
28. Bauer Br, Hartz AMS, Fricker G, 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
29. Geick A, Eichelbaum M, Burk O (2001) Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem 276:14581–14587. doi:10.1074/jbc.M010173200
30. Lehmann JrM, McKee DD, Watson MA, Willson TM, Moore JT, 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. doi:10.1172/JCI3703
31. Vogelgesang S, Cascorbi I, Schroeder E, Pahnke J, Kroemer HK, Siegmund W, Kunert-Keil C, Walker LC, Warzok RW (2002) Deposition of Alzheimer’s [beta]-amyloid is inversely correlated with P-glycoprotein expression in the brains of elderly non-demented humans. Pharmacogenet Genomics 12:535–541
32. Cordon-Cardo C, O’Brien JP, Casals D, Rittman-Grauer L, Biedler JL, Melamed MR, Bertino JR (1989) Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood–brain barrier sites. Proc Natl Acad Sci USA 86:695–698
33. Potschka H, Fedrowitz M, Loscher W (2002) P-Glycoprotein-mediated efflux of phenobarbital, lamotrigine, and felbamate at the blood brain barrier: Evidence from microdialysis experiments in rats. Neurosci Lett 327:173–176. doi:10.1016/S0304-3940(02)00423-8
34. Bendayan R, Ronaldson PT, Gingras D, Bendayan M (2006) In situ localization of P-glycoprotein (ABCB1) in human and rat brain. J Histochem Cytochem 54:1159–1167. doi:10.1369/jhc.5A6870.2006
35. van Assema Lubberink M, Bauer M, van der Flier WM, Schuit RC, Windhorst AD, Comans EFI, Hoetjes NJ, Tolboom N, Langer O (2012) Blood brain barrier P-glycoprotein function in Alzheimer’s disease. Brain 135:181–189. doi:10.1093/brain/awr298
36. Cirrito JR, Deane R, Fagan AM, Spinner ML, Parsadanian M, Finn MB, Jiang H, Prior JL, Sagare A, Bales KR (2005) P-glycoprotein deficiency at the blood–brain barrier increases amyloid-$$\beta $$β deposition in an Alzheimer disease mouse model. J Clin Invest 115:3285–3290. doi: 10.1172/JCI25247
37. Brenn A, Grube M, Peters M, Fischer A, Jedlitschky G, Kroemer HK, Warzok RW, Vogelgesang S (2011) Beta-amyloid downregulates MDR1-P-glycoprotein (Abcb1) expression at the blood–brain barrier in mice. Int J Alzheimer’s Dis 2011:1–6. doi:10.4061/2011/690121
38. Vogelgesang S, Warzok RW, Cascorbi I, Kunert-Keil C, Schroeder E, Kroemer HK, Siegmund W, Walker LC, Pahnke J (2004) The role of P-glycoprotein in cerebral amyloid angiopathy; implications for the early pathogenesis of Alzheimers disease. Curr Alzheimer Res 1:121–125. doi:10.2174/1567205043332225
39. Breier A, Gibalova L, Seres M, Barancik M, Sulova Z (2013) New Insight into P-glycoprotein as a drug target. Anti-Cancer Agent Med Chem 13:159–170. doi:10.2174/187152013804487380
40. Bauer Br, Yang X, Hartz AMS, Olson ER, Zhao R, Kalvass JC, Pollack GM, Miller DS (2006) In vivo activation of human pregnane X receptor tightens the blood–brain barrier to methadone through P-glycoprotein up-regulation. Mol Pharmacol 70:1212–1219. doi:10.1124/mol.106.023796
41. Ott M, Fricker G, Bauer Br (2009) Pregnane X receptor (PXR) regulates P-glycoprotein at the blood–brain barrier: Functional similarities between pig and human PXR. J Pharmacol Exp Ther 329:141–149. doi:10.1124/jpet.108.149690
42. Watkins RE, Davis-Searles PR, Lambert MH, Redinbo MR (2003) Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor. J Mol Biol 331:815–828. doi:10.1016/S0022-2836(03)00795-2
43. Synold TW, Dussault I, Forman BM (2001) The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med 7:584–590. doi:10.1038/87912
44. Jones SA, Moore LB, Shenk JL, Wisely GB, Hamilton GA, McKee DD, Tomkinson NCO, LeCluyse EL, Lambert MH, Willson TM (2000) The pregnane X receptor: A promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol 14:27–39. doi:10.4155/fmc.10.276
45. Tarcsay Á, Keseru GM (2011) Homology modeling and binding site assessment of the human P-glycoprotein. Future Med Chem 3:297–307. doi:10.4155/fmc.10.276
46. Watkins RE, Wisely GB, Moore LB, Collins JL, Lambert MH, Williams SP, Redinbo MR (2001) The human nuclear xenobiotic receptor PXR: Structural determinants of directed promiscuity. Science 292:2329–2333. doi:10.1126/science.1060762
47. Watkins RE, Maglich JM, Moore LB, Wisely GB, Noble SM, Davis-Searles PR, Redinbo MR (2003) 2.1 Å crystal structure of human PXR in complex with the St. John’s wort compound hyperforin. Biochemistry 42:1430–1438. doi:10.1021/bi0268753
48. Watkins RE, Davis-Searles PR, Lambert MH, Redinbo MR (2003) Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor. J Mol Biol 331:815–828. doi:10.1016/S0022-2836(03)00795-2
49. Chang G, Roth CB (2001) Structure of MsbA from E. coli: A homolog of the multidrug resistance ATP binding cassette (ABC) transporters. Science 293:1793–1800. doi:10.1126/science.293.5536.1793
50. Dawson RJP, Locher KP (2006) Structure of a bacterial multidrug ABC transporter. Nature 443:180–185. doi:10.1038/nature05155
51. Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G (2009) Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 323:1718–1722. doi:10.1126/science.1168750
52. Jin MS, Oldham ML, Zhang Q, Chen J (2012) Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans. Nature 490:566–569. doi:10.1038/nature11448
53. Prajapati R, Singh U, Patil A, Khomane KS, Bagul P, Bansal AK, Sangamwar AT (2013) In silico model for P-glycoprotein substrate prediction: Insights from molecular dynamics and in vitro studies. J Comput Aided Mol Des 27:347–363. doi:10.1007/s10822-013-9650-x
54. Watkins RE, Davis-Searles PR, Lambert MH, Redinbo MR (2003) Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor. J Mol Biol 331:815–828. doi:10.1016/S0022-2836(03)00795-2
55. Watkins RE, Maglich JM, Moore LB, Wisely GB, Noble SM, Davis-Searles PR, Lambert MH, Kliewer SA, Redinbo MR (2003) 2.1 Å crystal structure of human PXR in complex with the St. John’s wort compound hyperforin. Biochemistry 42:1430–1438. doi:10.1021/bi0268753
56. Watkins RE, Wisely GB, Moore LB, Collins JL, Lambert MH, Williams SP, Willson TM, Kliewer SA, Redinbo MR (2001) The human nuclear xenobiotic receptor PXR: Structural determinants of directed promiscuity. Science 292:2329–2333. doi:10.1126/science.1060762
57. Loo TW, Bartlett MC, Clarke DM (2003) Substrate-induced conformational changes in the transmembrane segments of human P-glycoprotein. J Biol Chem 278:13603–13606. doi:10.1074/jbc.C300073200
58. Callaghan R, Ford RC, Kerr ID (2006) The translocation mechanism of P-glycoprotein. FEBS Lett 580:1056–1063. doi:10.1016/j.febslet.2005.11.083
59. Constantinides PP, Wasan KM (2007) Lipid formulation strategies for enhancing intestinal transport and absorption of P-glycoprotein (Pgp) substrate drugs: In vitro/in vivo case studies. J Pharm Sci 96:235–248. doi:10.1002/jps.20780
60. Aisen PS (1996) Inflammation and Alzheimer disease. Mol Chem Neuropathol 28:83–88. doi:10.1007/BF02815208
61. Leung R, Proitsi P, Simmons A, Lunnon K, Gntert A, Kronenberg D, Pritchard M, Tsolaki M, Mecocci P, Kloszewska I (2013) Inflammatory proteins in plasma are associated with severity of Alzheimers disease. PLoS One 8:649–671. doi:10.1371/journal.pone.0064971
62. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL (2000) Inflammation and Alzheimers disease. Neurobiol Aging 21:383–421. doi:10.1016/S0197-4580(00)00124-X
63. Shah YM, Ma X, Morimura K, Kim I, Gonzalez FJ (2007) Pregnane X receptor activation ameliorates DSS-induced inflammatory bowel disease via inhibition of NF-kB target gene expression. Am J Physiol Gastrointest Liver Physiol 292:G1114–G1122. doi:10.1152/ajpgi.00528.2006
64. Langmade SJ, Gale SE, Frolov A, Mohri I, Suzuki K, Mellon SH, Walkley SU, Covey DF, Schaffer JE, Ory DS (2006) Pregnane X receptor (PXR) activation: A mechanism for neuroprotection in a mouse model of Niemann–Pick C disease. Proc Natl Acad Sci USA 103:13807–13812. doi:10.1073/pnas.0606218103
65. Wolf A, Bauer B, Hartz AMS (2012) ABC transporters and the Alzheimer’s disease enigma. Front Psychiatry 3:1–14. doi:10.3389/fpsyt.2012.00054
66. Löscher W, Potschka H (2005) Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci 6:591–602. doi:10.1038/nrn1728
67. Enokizono J, Kusuhara H, Sugiyama Y (2007) Effect of breast cancer resistance protein (Bcrp/Abcg2) on the disposition of phytoestrogens. Mol Pharmacol 72:967–975. doi:10.1124/mol.107.034751
68. Sharom FJ (2008) ABC multidrug transporters: Structure, function and role in chemoresistance. Pharmacogenomics 9:105–127. doi:10.2217/14622416.9.1.105
69. Eid SY, El-Readi MZ, Wink M (2012) arotenoids reverse multidrug resistance in cancer cells by interfering with ABC-transporters. Phytomedicine 19:977–987. doi:10.1016/j.phymed.2012.05.010
70. E-j Wang, Lew K, Casciano CN, Clement RP, Johnson WW (2002) Interaction of common azole antifungals with P glycoprotein. Antimicrob Agents Chem 46:160–165. doi:10.1128/AAC.46.1.160-165.2002
71. Maitrejean M, Comte G, Barron D, El Kirat K, Di Pietro A (2000) The flavanolignan silybin and its hemisynthetic derivatives, a novel series of potential modulators of P-glycoprotein. Bioorg Med Chem Lett 10:157–160. doi:10.1016/S0960-894X(99)00636-8
72. Kis E, Nagy T, Jani M, Molnár E, Jánossy J, Ujhellyi O, Német K, Herédi-Szabó K, Krajcsi P (2009) Leflunomide and its metabolite A771726 are high affinity substrates of BCRP: Implications for drug resistance. Ann Rheum Dis 68:1201–1207. doi:10.1136/ard.2007.086264
73. Nabekura T, Yamaki T, Ueno K, Kitagawa S (2008) Inhibition of P-glycoprotein and multidrug resistance protein 1 by dietary phytochemicals. Cancer Chemother Pharmacol 62:867–873. doi:10.1007/s00280-007-0676-4
74. El-Readi MZ, Hamdan D, Farrag N, El-Shazly A, Wink M (2010) Inhibition of P-glycoprotein activity by limonin and other secondary metabolites from Citrus species in human colon and leukaemia cell lines. Eur J Pharmacol 626:139–145. doi:10.1016/j.ejphar.2009.09.040
75. von Moltke LL, Weemhoff JL, Perloff MD, Hesse LM, Harmatz JS, Roth-Schechter BF, Greenblatt DJ (2002) Effect of zolpidem on human cytochrome P450 activity, and on transport mediated by P-glycoprotein. Biopharm Drug Dispos 23:361–367. doi:10.1002/bdd.329
76. Hennessy M, Kelleher D, Spiers JP, Barry M, Kavanagh P, Back D, Mulcahy F, Feely J (2002) St John’s Wort increases expression of P-glycoprotein: Implications for drug interactions. Br J Clin Pharmacol 53:75–82. doi:10.1046/j.0306-5251.2001.01516.x
77. Perloff MD, Von Moltke LL, Stormer E, Shader RI, Greenblatt DJ (2001) Saint John’s wort: An in vitro analysis of P-glycoprotein induction due to extended exposure. Br J Pharmacol 134:1601–1608. doi:10.1038/sj.bjp.0704399
78. Ott M, Huls M, Cornelius M, Fricker G (2010) St. John’s wort constituents modulate P-glycoprotein transport activity at the blood–brain barrier. Pharm Res 27:811–822. doi:10.1007/s11095-010-0074-1
79. Fromm MF (2004) Importance of P-glycoprotein at blood–tissue barriers. Trends Pharmacol Sci 25:423–429. doi:10.1016/j.tips.2004.06.002
80. Shen X, Chen G, Zhu G, Fong W-F (2006) ($$\pm $$±)-3$$^\prime $$′-O,4$$^\prime $$′-O-dicynnamoyl-cis-khellactone, a derivative of ($$\pm)$$±)-praeruptorin A, reverses P-glycoprotein mediated multidrug resistance in cancer cells. Bioorg Med Chem Lett 14:7138–7145. doi: 10.1016/j.bmc.2006.06.066
81. Sparreboom A, Van Asperen J, Mayer U, Schinkel AH, Smit JW, Meijer DKF, Borst P, Nooijen WJ, Beijnen JH, Van Tellingen O (1997) Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci India A/B 94:2031–2035
82. Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF (2002) Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 302:645–650. doi:10.1124/jpet.102.034728
83. Polli JW, Jarrett JL, Studenberg SD, Humphreys JE, Dennis SW, Brouwer KR, Woolley JL (1999) Role of P-glycoprotein on the CNS disposition of amprenavir (141W94), an HIV protease inhibitor. Pharm Res 16:1206–1212. doi:10.1023/A:1018941328702
84. Wang E-j, Barecki-Roach M, Johnson WW (2004) Quantitative characterization of direct P-glycoprotein inhibition by St John’s wort constituents hypericin and hyperforin. J Pharm Pharmacol 56:123–128. doi:10.1211/0022357022395
85. Potschka H, Fedrowitz M, Loscher W (2001) P-glycoprotein and multidrug resistance-associated protein are involved in the regulation of extracellular levels of the major antiepileptic drug carbamazepine in the brain. Neuroreport 12:3557 –3560
86. Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y (2009) Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci 100:1701–1707. doi:10.1111/j.1349-7006.2009.01213.x
87. Ueda K, Okamura N, Hirai M, Tanigawara Y, Saeki T, Kioka N, Komano T, Hori R (1992) Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. J Biol Chem 267:24248–24252
88. Yasuda K, Lan L-b, Sanglard D, Furuya K, Schuetz JD, Schuetz EG (2002) Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther 303:323–332. doi:10.1124/jpet.102.037549
89. Perloff MD, Stormer E, von Moltke LL, Greenblatt DJ (2003) Rapid assessment of P-glycoprotein inhibition and induction in vitro. Pharm Res 20:1177–1183. doi:10.1023/A:1025092829696
90. Potschka H, Fedrowitz M, Loscher W (2002) P-glycoprotein-mediated efflux of phenobarbital, lamotrigine, and felbamate at the blood–barrier: Evidence from microdialysis experiments in rats. Neurosci Lett 327:173–176. doi:10.1016/S0304-3940(02)00423-8
91. Robert J, Jarry C (2003) Multidrug resistance reversal agents. J Med Chem 46:4805–4817. doi:10.1021/jm030183a
92. Relling MV (1996) Are the major effects of P-glycoprotein modulators due to altered pharmacokinetics of anticancer drugs? Ther Drug Monit 18:350–356
93. Wasserman L, Aviram R, Levavi H, Ovadia J, Shneyuor Y, Frisch A, Blau O, Beery E, Novogrodsky A, Nordenberg J (1992) A cell line with unusual characteristics from an ovarian carcinoma patient: Modulation of sensitivity to antitumour drugs. Eur J Cancer 28:22–27. doi:10.1016/0959-8049(92)90376-D
94. Schuetz EG, Beck WT, Schuetz JD (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
95. Xin HW, Wu XC, Li Q, Yu AR, Zhu M, Shen Y, Su D, Xiong L (2007) Effects of Schisandra sphenanthera extract on the pharmacokinetics of tacrolimus in healthy volunteers. Br J Clin Pharmacol 64:469–475. doi:10.1111/j.1365-2125.2007.02922.x
96. Kim RB (2002) Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab Rev 34:47–54. doi:10.1081/DMR-120001389
97. Dimitroulakos J, Yeger H (1996) HMG-CoA reductase mediates the biological effects of retinoic acid on human neuroblastoma cells: lovastatin specifically targets P-glycoprotein-expressing cells. Nat Med 2:326–333. doi:10.1038/nm0396-326
98. Li D-Q, Wang Z-B, Bai J, Zhao J, Wang Y, Hu K, Du Y-H (2004) Reversal of multidrug resistance in drug-resistant human gastric cancer cell line SGC7901/VCR by antiprogestin drug mifepristone. World J Gastroenterol 10:1722–1725
99. Balakrishnan B, Henare K, Thorstensen EB, Ponnampalam AP, Mitchell MD (2010) Transfer of bisphenol A across the human placenta. Am J Obstet Gynacol 202:393–397. doi:10.1016/j.ajog.2010.01.025
100. Ichikawa-Haraguchi M, Sumizawa T, Yoshimura A, Furukawa T, Hiramoto S, Sugita M (1993) Progesterone and its metabolites: the potent inhibitors of the transporting activity of P-glycoprotein in the adrenal gland. Biochim Biophys Acta 1158:201–208. doi:10.1016/0304-4165(93)90016-2
101. Kivisto KT, Zukunft J, Hofmann U, Niemi M, Rekersbrink S, Schneider S, Luippold G, Schwab M, Eichelbaum M, Fromm MF (2004) Characterisation of cerivastatin as a P-glycoprotein substrate: Studies in P-glycoprotein-expressing cell monolayers and mdr1a/b knock-out mice. Naunyn Schmiedebergs Arch Pharmacol 370:124–130. doi:10.1007/s00210-004-0948-z
102. Bekaii-Saab TS, Perloff MD, Weemhoff JL, Greenblatt DJ, von Moltke LL (2004) Interactions of tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen with P-glycoprotein and CYP3A. Biopharm Drug Dispos 25:283–289. doi:10.1002/bdd.411
103. Konings WN, Poelarends GJ (2002) Bacterial multidrug resistance mediated by a homologue of the human multidrug transporter P-glycoprotein. IUBMB Life 53:213–218. doi:10.1080/15216540212646
104. Susanto M, Benet LZ (2002) Can the enhanced renal clearance of antibiotics in cystic fibrosis patients be explained by P-glycoprotein transport? Pharm Res 19:457–462. doi:10.1023/A:1015191511817
105. X-f Zhou, Zhang L, Tseng E, Scott-Ramsay E, Schentag JJ, Coburn RA, Morris ME (2005) New 4-aryl-1, 4-dihydropyridines and 4-arylpyridines as P-glycoprotein inhibitors. Drug Metab Dispos 33:321–328. doi:10.1124/dmd.104.00208
106. Wils P, Phung-Ba Vr, Warnery A, Lechardeur D, Raeissi S, Hidalgo IJ, Scherman D (1994) Polarized transport of docetaxel and vinblastine mediated by P-glycoprotein in human intestinal epithelial cell monolayers. Biochem Pharmacol 48:1528–1530. doi:10.1016/0006-2952(94)90580-0
107. Aungst BJ (1999) P-glycoprotein, secretory transport, and other barriers to the oral delivery of anti-HIV drugs. Adv Drug Deliv Rev 39:105–116. doi:10.1016/S0169-409X(99)00022-8
108. Lentz K, Polli J, Wring S, Humphreys J, Polli J (2000) Influence of passive permeability on apparent P-glycoprotein kinetics. Pharm Res 17:1456–1460. doi:10.1023/a:1007692622216
109. Bain LJ, Leblanc GA (1996) Interaction of structurally diverse pesticides with the human MDR1 gene product P-glycoprotein. Toxicol Appl Pharm 141:288–298. doi:10.1006/taap.1996.0286
110. Barnes KM, Dickstein B, Cutler GB, Fojo T, Bates SE (1996) Steroid transport, accumulation, and antagonism of P-glycoprotein in multidrug-resistant cells. Biochemistry 35:4820–4827. doi:10.1021/bi952380k
111. Kodaira H, Kusuhara H, Ushiki J, Fuse E, Sugiyama Y (2010) Kinetic analysis of the cooperation of P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (Bcrp/Abcg2) in limiting the brain and testis penetration of erlotinib, flavopiridol, and mitoxantrone. J Pharmacol Exp Ther 333:788–796. doi:10.1124/jpet.109.162321
112. Holtzman CW, Wiggins BS, Spinler SA (2006) Role of P-glycoprotein in statin drug interactions. Pharmacotherapy 26:1601–1607. doi:10.1592/phco.26.11.1601
113. Najar IA, Sachin BS, Sharma SC, Satti NK, Suri KA, Johri RK (2010) Modulation of P-glycoprotein ATPase activity by some phytoconstituents. Phytother Res 24:454–458. doi:10.1002/ptr.2951
114. Sreeramulu K, Liu R, Sharom FJ (2007) Interaction of insecticides with mammalian P-glycoprotein and their effect on its transport function. Biochim Biophys Acta 1768:1750–1757. doi:10.1016/j.bbamem.2007.04.001
115. Frohlich M, Albermann N, Sauer A, Walter-Sack I, Haefeli WE, Weiss J (2004) In vitro and ex vivo evidence for modulation of P-glycoprotein activity by progestins. Biochem Pharmacol 68:2409–2416. doi:10.1016/j.bcp.2004.08.026
116. Shabbir A, DiStasio S, Zhao J, Cardozo CP, Wolff MS, Caplan AJ (2005) Differential effects of the organochlorine pesticide DDT and its metabolite p,p$$^{\prime }$$′-DDE on p-glycoprotein activity and expression. Toxicol Appl Pharm 203:91–98. doi: 10.1016/j.taap.2004.07.011
117. Gosland M, Tsuboi C, Hoffman T, Goodin S, Vore M (1993) 17$$\beta $$β-Estradiol glucuronide: An inducer of cholestasis and a physiological substrate for the multidrug resistance transporter. Cancer Res 53:5382–5385
118. Giacomini KM, Huang S-M, Tweedie DJ, Benet LZ, Brouwer KLR, Chu X, Dahlin A, Evers R, Fischer V, Hillgren KM (2010) Membrane transporters in drug development. Nat Rev Drug Discov 9:215–236. doi:10.1038/nrd3028
119. Katoh M, Nakajima M, Yamazaki H, Yokoi T (2000) Inhibitory potencies of 1,4-dihydropyridine calcium antagonists to P-glycoprotein-mediated transport: comparison with the effects on CYP3A4. Pharm Res 17:1189–1197. doi:10.1023/A:1007568811691
120. Wu X, Whitfield LR, Stewart BH (2000) Atorvastatin transport in the Caco-2 cell model: contributions of P-glycoprotein and the proton-monocarboxylic acid co-transporter. Pharm Res 17:209–215. doi:10.1023/A:1007525616017
121. E-j Wang, Lew K, Barecki M, Casciano CN, Clement RP, Johnson WW (2001) Quantitative distinctions of active site molecular recognition by P-glycoprotein and cytochrome P450 3A4. Chem Res Toxicol 14:1596–1603. doi:10.1021/tx010125x
122. Lanning CL (1996) Chlorpyrifos oxon interacts with the mammalian multidrug resistance protein, P-glycoprotein. J Toxicol Environ Health 47:95–407. doi:10.1080/009841096161726
123. Boyd RA, Stern RH, Stewart BH, Wu X, Reyner EL, Zegarac EA, Randinitis EJ, Whitfield L (2000) Atorvastatin coadministration may increase digoxin concentrations by inhibition of intestinal P-glycoprotein mediated secretion. J Clin Pharmacol 40:91–98. doi:10.1177/009127000004000112
124. Wadelius M, Sorlin K, Wallerman O, Karlsson J, Yue QY, Magnusson PKE, Wadelius C (2003) Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors. Pharmacogenomics J 4:40–48. doi:10.1038/sj.tpj.6500220
125. Zhang J, Huang M, Guan S, Bi H-C, Pan Y, Duan W, Chan SY, Chen X, Hong Y-H, Bian J-S (2006) A mechanistic study of the intestinal absorption of cryptotanshinone, the major active constituent of Salvia miltiorrhiza. J Pharmacol Exp Ther 317:1285–1294. doi:10.1124/jpet.105.10070
126. Buss DS, McCaffery AR, Callaghan A (2002) Evidence for p-glycoprotein modification of insecticide toxicity in mosquitoes of the Culex pipiens complex. Med Vet Entomol 16:218–222. doi:10.1046/j.1365-2915.2002.00365.x
127. Eufemia NA, Epel D (2000) Induction of the multixenobiotic defense mechanism (MXR), P-glycoprotein, in the mussel Mytilus californianus as a general cellular response to environmental stresses. Aquat Toxicol 49:89–100. doi:10.1016/S0166-445X(99)00068-5
128. Fedoruk MN, Gimenez-Bonafe P, Guns ES, Mayer LD, Nelson CC (2004) P-glycoprotein increases the efflux of the androgen dihydrotestosterone and reduces androgen responsive gene activity in prostate tumor cells. Prostate 59:77–90. doi:10.1002/pros.10354
129. Wang EJ, Casciano CN, Clement RP, Johnson WW (2001) HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors of P-glycoprotein. Pharm Res 18:800–806. doi:10.1023/A:1011036428972
130. Takano M, Hasegawa R, Fukuda T, Yumoto R, Nagai J, Murakami T (1998) Interaction with P-glycoprotein and transport of erythromycin, midazolam and ketoconazole in Caco-2 cells. Eur J Pharmcol 358:289–294. doi:10.1016/S0014-2999(98)00607-4
131. El-Readi MZ, Hamdan D, Farrag N, El-Shazly A, Wink M (2010) Inhibition of P-glycoprotein activity by limonin and other secondary metabolites from Citrus species in human colon and leukaemia cell lines. Eur J Pharmcol 626:139–145. doi:10.1016/j.ejphar.2009.09.040