Downregulation of mdr1a expression in the brain and liver during CNS inflammation alters the in vivo disposition of digoxin

British Journal of Pharmacology

Volumn 139, Issue 1, 2003, Pages 35-48

  Goralski, Kerry B ^a   Hartmann, Georgy ^b   Piquette Miller, Micheline ^b   Renton, Kenneth W ^a  

^a DALHOUSIE UNIVERSITY   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

CNS inflammation; Digoxin; Drug elimination; Drug transport; Mdr1; Organic anion transporting polypeptide (oatp2); P glycoprotein

Indexed keywords

CYCLOSPORIN A; DIGOXIN; ESCHERICHIA COLI LIPOPOLYSACCHARIDE; GLYCOPROTEIN P; MESSENGER RNA; SODIUM CHLORIDE;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG DISPOSITION; DRUG ELIMINATION; DRUG MECHANISM; ENCEPHALITIS; IMMUNOHISTOCHEMISTRY; IN VIVO STUDY; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT;

ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; BILE; BRAIN; DIGOXIN; DOWN-REGULATION; ENCEPHALITIS; ESCHERICHIA COLI; FEMALE; IMMUNOHISTOCHEMISTRY; INTESTINES; LIPOPOLYSACCHARIDES; LIVER; MALE; MICE; MICE, MUTANT STRAINS; ORGANIC CATION TRANSPORT PROTEINS; P-GLYCOPROTEINS; RATS; RATS, SPRAGUE-DAWLEY; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; TISSUE DISTRIBUTION;

EID: 0037716531     PISSN: 00071188     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.bjp.0705227     Document Type: Article

References (45)

1. ANDO, H., NISHIO, Y., ITO, K., NAKAO, A., WANG. L., ZHAO, Y.L., KITAICHI, K., TAKAGI, K. & HASEGAWA, T. (2001). Effect of endotoxin on P-glycoprotein-mediated biliary and renal excretion of rhodamine-123 in rats. Antimicrob. Agents. Chemother.. 45, 3462-3467.
2. BEAULIEU, E., DEMEULE, M., GHITESCU, L. & BELIVEAU, R. (1997). P-glycoprotein is strongly expressed in the luminal membranes of the endothelium of blood vessels in the brain. Biochem. J., 326, 539-544.
3. CARVALHAS, M.L. & FIGUEIRA, M.A. (1973). Comparative study of thin-layer chromatographic techniques for separation of digoxin, digitoxin and their main metabolites. J. Chromatogr., 86, 254-260.
4. CATTORI, V., VAN MONTFOORT, J.E., STIEGER, B., LANDMANN, L., MEIJER, D.K., WINTERHALTER, K.H., MEIER, P.J. & HAGENBUCH, B. (2001). Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3. Pflugers Arch., 443, 188-195.
5. CROOP, J.M., RAYMOND, M., HABER, D., DEVAULT, A., ARCECI, R.J., GROS, P. & HOUSMAN, D.E. (1989). The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues. Mol. Cell Biol., 9, 1346-1350.
6. DE VRIES, H.E., KUIPER, J., DE BOER, A.G., VAN BERKEL, T.J. & BREIMER, D.D. (1997). The blood - brain barrier in neuroinflammatory diseases. Pharmacol. Rev., 49, 143-155.
7. DRACH, J., GSUR, A., HAMILTON, G., ZHAO, S., ANGERLER, J., FIEGL, M., ZOJER, N., RADERER, M., HABERL, I., ANDREEFF, M. & HUBER, H. (1996). Involvement of P-glycoprotein in the transmembrane transport of interleukin-2 (IL-2), IL-4, and interferon-gamma in normal human T lymphocytes. Blood, 88, 1747-1754.
8. FRANKLIN, K.B.J. & PAXINOS, G. (1997). The Mouse Brain in Stereotaxic Coordinates. San Diego: Academic Press.
9. GAO, B., STIEGER, B., NOE, B., FRITSCHY, J.M. & MEIER, P.J. (1999). Localization of the organic anion transporting polypeptide 2 (Oatp2) in capillary endothelium and choroid plexus epithelium of rat brain. J. Histochem. Cytochem., 47, 1255-1264.
10. GONZALEZ-SCARANO, F. & BALTUCH, G. (1999). Microglia as mediators of inflammatory and degenerative diseases. Annu. Rev. Neurosci., 22, 219-240.
11. GOTTESMAN, MM. & PASTAN, I. (1993). Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem., 62, 385-427.
12. HARRISON, L.I. &, GIBALDI, M. (1976). Pharmacokinetics of digoxin in the rat. Drug Metab. Dispos., 4, 88-93.
13. HARTMANN, G., KIM, H. & PIQUETTE-MILLER, M. (2001). Regulation of the hepatic multidrug resistance gene expression by endotoxin and inflammatory cytokines in mice. Int. Immunopharmacol., 1, 189-199.
14. JOHNSON, D.R., FINCH, R.A., LIN, Z.P., ZEISS, C.J. & SARTORELLI, A.C. (2001). The pharmacological phenotype of combined multi-drug-resistance mdr1/Ib and mrpI-deficient mice. Cancer Res., 61, 1469-1476.
15. JOHNSTONE, R.W., RUEFLI, A.A. & SMYTH, M.J. (2000). Multiple physiological functions for multidrug transporter P- glycoprotein? Trends Biochem. Sci., 25, 1-6.
16. KAWAHARA, M., SAKATA, A., MIYASHITA, T., TAMAI, I. & TSUJI, A. (1999). Physiologically based pharmacokinetics of digoxin in mdrla knockout mice. J. Pharm. Sci., 88, 1281-1287.
17. KODAWARA, T., MASUDA, S., WAKASUGI, H., UWAI, Y., FUTAMI, T., SAITO, H., ABE, T. & INU, K. (2002). Organic anion transporter oatp2-mediated interaction between digoxin and amiodarone in the rat liver. Pharm. Res., 19, 738-743.
18. MAYER, U., WAGENAAR, E., BEIJNEN, J.H., SMIT, J.W., MEIJER, D.K., VAN ASPEREN, J., BORST, P. & SCHINKEL, A.H. (1996). Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr Ia P-glycoprotein. Br. J. Pharmacol., 119, 1038-1044.
19. MEIJER, O.C., DE LANGE, E.C., BREIMER, D.D., DE BOER, A.G., WORKEL, J.O. & DE KLOET, E.R. (1998). Penetration of dexamethasone into brain glucocorticoid targets is enhanced in mdrlA P-glycoprotein knockout mice. Endocrinology, 139, 1789-1793.
20. MILLER, D.S., SUSSMAN, C.R. & RENFRO, J.L. (1998). Protein kinase C regulation of p-glycoprotein-mediated xenobiotic secretion in renal proximal tubule. Am. J. Physiol., 275, F785-F795.
21. MORGAN, E.T. (2001). Regulation of cytochrome p450 by inflammatory mediators: why and how? Drug Metab. Dispos., 29, 207-212.
22. NADEAU, S. & RIVEST, S. (2002). Endotoxemia prevents the cerebral inflammatory wave induced by intraparenchymal lipopolysaccharide injection: role of glucocorticoids and CD14. J. Immunol., 169, 3370-3381.
23. NICHOLSON, T.E. & RENTON, K.W. (2001). Role of cytokines in the lipopolysaccharide-evoked depression of cytochrome P450 in the brain and liver. Biochem. Pharmacol., 62, 1709-1717.
24. NOE, B., HAGENBUCH, B., STIEGER, B. & MEIER, P.J. (1997). Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain. Proc. Natl. Acad. Sci. U.S.A., 94, 10346-10350.
25. PANWALA, C.M., JONES, J.C. & VINEY, J.L. (1998). A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1, spontaneously develop colitis. J. Immunol., 161, 5733-5744.
26. PAXINOS, G. & WATSON, C. (1986). The Rat Brain in Stereotaxic Coordinates. Sydney: Academic Press.
27. PERRY, V.H., ANDERSSON, P.B. & GORDON, S. (1993). Macrophages and inflammation in the central nervous system. Trends Neurosci., 16, 268-273.
28. PIQUETTE-MILLER, M., PAK, A., KIM, H., ANARI, R. & SHAHZAMANI, A. (1998). Decreased expression and activity of P-glycoprotein in rat liver during acute inflammation. Pharm Res., 15, 706-711.
29. RAO, V.V., DAHLHEIMER, J.L., BARDGETT, M.E., SNYDER, A.Z., FINCH, R.A., SARTORELLI, A.C. & PIWNICA-WORMS, D. (1999). Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood cerebrospinal-fluid drug-permeability barrier. Proc. Natl. Acad. Sci. U.S.A., 96, 3900-3905.
30. REICHEL, C., GAO, B., VAN MONTFOORT, J., CATTORI, V., RAHNER, C., HAGENBUCH, B., STIEGER, B., KAMISAKO, T. & MEIER, P.J. (1999). Localization and function of the organic anion-transporting polypeptide Oatp2 in rat liver. Gastroenterology, 117, 688-695.
31. RENTON, K.W. (2000). Hepatic drug metabolism and immunostimulation. Toxicology, 142, 173-178.
32. RENTON, K.W. & NICHOLSON, T.E. (2000). Hepatic and central nervous system cytochrome P450 are down-regulated during lipopolysaccharide-evoked localized inflammation in brain. J. Pharmacol. Exp. Ther., 294, 524-530.
33. SALPHATI, L. & BENET, L.Z. (1999). Metabolism of digoxin and digoxigenin digitoxosides in rat liver microsomes: involvement of cytochrome P4503A. Xenobiotica, 29, 171-185.
34. SCHELD, W.M., KOEDEL, U., NATHAN, B., & PFISTER, H.W. (2002). Pathophysiology of bacterial meningitis: mechanism(s) of neuronal injury. J. Infect. Dis., 186(Suppl. 2), S225-S233.
35. SCHINKEL, A.H., MAYER, U., WAGENAAR, E., MOL, C.A., VAN DEEMTER, L., SMIT, J.J., VAN DER VALK, M.A., VOORDOUW, A.C., SPITS, H., VAN TELLINGEN, O., ZIJLMANS, J.M., FIBBE, W.E. & BORST, P. (1997). Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc. Natl. Acact Sci. U.S.A., 94, 4028-4033.
36. SCHINKEL, A.H., SMIT, J.J., VAN TELLINGEN, O., BEIJNEN, J.H., WAGENAAR, E., VAN DEEMTER, L., MOL, C.A., VAN DER VALK, M.A., ROBANUS-MAANDAG, E.C. & TE RIELE, H.P. (1994). Disruption of the mouse mdr1 a P-glycoprotein gene leads to a deficiency in the blood - brain barrier and to increased sensitivity to drugs. Cell, 77, 491-502.
37. SCHINKEL, A.H., WAGENAAR, E., VAN DEEMTER, L., MOL, C.A. & BORST, P. (1995). Absence of the mdr1a P-glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J. Clin. Invest., 96, 1698-1705.
38. SUKHAI, M., YONG, A., PAK, A. & PIQUETTE-MILLER, M. (2001). Decreased expression of P-glycoprotein in interleukin-1beta and interleukin-6 treated rat hepatocytes. Inflamm Res, 50, 362-370.
39. TEPPERMAN, B.L., CHANG, Q. & SOPER, B.D. (2000). Protein kinase C mediates lipopolysaccharide- and phorbol-induced nitric-oxide synthase activity and cellular injury in the rat colon. J. Pharmacol. Exp. Ther., 295, 1249-1257.
40. TSURUOKA, S., SUGIMOTO, K.I., FUJIMURA, A., IMAI, M., ASANO, Y. & MUTO, S. (2001). P-glycoprotein-mediated drug secretion in mouse proximal tubule perfused in vitro. J. Am. Soc. Nephrol., 12, 177-181.
41. VAN ASPEREN, J., VAN TELLINGEN, O. & BEIJNEN, J.H. (2000). The role of mdr1a P-glycoprotein in the biliary and intestinal secretion of doxorubicin and vinblastine in mice. Drug Metab. Dispos., 28, 264-267.
42. VOS, T.A., HOOIVELD, G.J., KONING, H., CHILDS, S., MEIJER, D.K., MOSHAGE, H., JANSEN, P.L. & MULLER, M. (1998), Upregulation of the multidrug resistance genes, Mrp1 and Mdr1b, and down-regulation of the organic anion transporter, Mrp2, and the bile salt transporter, Spgp, in endotoxemic rat liver. Hepatology, 28, 1637-1644.
43. WOLF, D.C. & HORWlTZ, S.B. (1992). P-glycoprotein transports corticosterone and is photoaffinity-labeled by the steroid. Int. J. Cancer, 52, 141-146.
44. ZHANG, W. & LING, V. (2000). Cell-cycle-dependent turnover of P-glycoprotein in multidrug-resistant cells. J. Cell Physiol., 184, 17-26.
45. ZHAO, Y.L., DU, J., KANAZAWA, H., SUGAWARA, A., TAKAGI, K., KITAICHI, K., TATSUMI, Y., HASEGAWA, T. (2002). Effect of endotoxin on doxorubicin transport across blood-brain barrier and P-glycoprotein function in mice. Eur. J. Pharmacol., 445, 115-123.