![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 300, Issue 1, 97-104, January 2002
University of Kansas Medical Center, Kansas City, Kansas
Many phase I and II microsomal enzyme inducers share common mechanisms
of transcriptional activation and thus share a similar battery of genes
that are coordinately regulated. Many phase II metabolites are
thought to be transported out of cells by multidrug resistance proteins
1, 2, and 3 (Mrp1, 2, and 3). The purpose of this study was to
determine the organ distribution of these three transporters in rat,
and whether they are coordinately regulated with phase I and II
drug-metabolizing enzymes. Therefore, Mrp1, 2, and 3 mRNAs were
quantified using branched DNA signal amplification in multiple tissues
and in tissues from rats that were treated with 18 chemicals thought to
induce drug-metabolizing enzymes by six different transcription
activation mechanisms [aryl-hydrocarbon receptor ligands, constitutive
androstane receptor (CAR) activators, pregnane-X-receptor ligands,
peroxisome proliferator activator receptor ligands, electrophile
response element (EpRE) activators, and CYP2E1 inducers]. It was found
that Mrp1 was expressed at a high level in kidney, lung, intestine, and
brain, with low expression in liver. Mrp2 was highly expressed in liver
and duodenum, and Mrp3 was highly expressed throughout the intestine
but very low in liver. Microsomal enzyme inducers did not markedly
increase the expression of Mrp1 or Mrp2. However, Mrp3 expression was
significantly increased by each of the CAR activators and an EpRE
activator in liver. Mrp3 was not similarly induced in kidney and large
intestine, demonstrating that the coordinate inducibility of Mrp3 is
specific to the liver. We conclude that rat hepatic Mrp3 is induced by CAR activators, thus enhancing the vectoral excretion of some phase II
metabolites from the liver to the blood.
This article has been cited by other articles:
|
|
 |
|
  C. MacLean, U. Moenning, A. Reichel, and G. Fricker Closing the Gaps: A Full Scan of the Intestinal Expression of P-Glycoprotein, Breast Cancer Resistance Protein, and Multidrug Resistance-Associated Protein 2 in Male and Female Rats Drug Metab. Dispos., July 1, 2008; 36(7): 1249 - 1254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. Beilke, D. G. Besselsen, Q. Cheng, S. Kulkarni, A. L. Slitt, and N. J. Cherrington Minimal Role of Hepatic Transporters in the Hepatoprotection against LCA-Induced Intrahepatic Cholestasis Toxicol. Sci., March 1, 2008; 102(1): 196 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Callaghan, E. Crowley, S. Potter, and I. D. Kerr P-glycoprotein: So Many Ways to Turn It On J. Clin. Pharmacol., March 1, 2008; 48(3): 365 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tanaka, C. Chen, J. M. Maher, and C. D. Klaassen Ischemia-Reperfusion of Rat Livers Decreases Liver and Increases Kidney Multidrug Resistance Associated Protein 2 (Mrp2) Toxicol. Sci., January 1, 2008; 101(1): 171 - 178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Petrick and C. D. Klaassen Importance of Hepatic Induction of Constitutive Androstane Receptor and Other Transcription Factors That Regulate Xenobiotic Metabolism and Transport Drug Metab. Dispos., October 1, 2007; 35(10): 1806 - 1815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Lickteig, C. D. Fisher, L. M. Augustine, L. M. Aleksunes, D. G. Besselsen, A. L. Slitt, J. E. Manautou, and N. J. Cherrington Efflux Transporter Expression and Acetaminophen Metabolite Excretion Are Altered in Rodent Models of Nonalcoholic Fatty Liver Disease Drug Metab. Dispos., October 1, 2007; 35(10): 1970 - 1978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kobayashi, A. Tsuchiya, T. Hayashi, N. Kohyama, M. Ohbayashi, and T. Yamamoto Isolation and Characterization of Polyspecific Mouse Organic Solute Carrier Protein 1 (mOscp1) Drug Metab. Dispos., July 1, 2007; 35(7): 1239 - 1245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Fisher, L. M. Augustine, J. M. Maher, D. M. Nelson, A. L. Slitt, C. D. Klaassen, L. D. Lehman-McKeeman, and N. J. Cherrington Induction of Drug-Metabolizing Enzymes by Garlic and Allyl Sulfide Compounds via Activation of Constitutive Androstane Receptor and Nuclear Factor E2-Related Factor 2 Drug Metab. Dispos., June 1, 2007; 35(6): 995 - 1000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yamazaki, S. Kakizaki, N. Horiguchi, N. Sohara, K. Sato, H. Takagi, M. Mori, and M. Negishi The role of the nuclear receptor constitutive androstane receptor in the pathogenesis of non-alcoholic steatohepatitis Gut, April 1, 2007; 56(4): 565 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tanaka, J. M. Maher, C. Chen, and C. D. Klaassen Hepatic Ischemia-Reperfusion Induces Renal Heme Oxygenase-1 via NF-E2-Related Factor 2 in Rats and Mice Mol. Pharmacol., March 1, 2007; 71(3): 817 - 825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. N. C. Gropp, D. L. Greger, C. Morel, S. Sauter, and J. W. Blum Nuclear receptor and nuclear receptor target gene messenger ribonucleic acid levels at different sites of the gastrointestinal tract and in liver of healthy dogs J Anim Sci, October 1, 2006; 84(10): 2684 - 2691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Slitt, N. J. Cherrington, C. D. Fisher, M. Negishi, and C. D. Klaassen INDUCTION OF GENES FOR METABOLISM AND TRANSPORT BY TRANS-STILBENE OXIDE IN LIVERS OF SPRAGUE-DAWLEY AND WISTAR-KYOTO RATS Drug Metab. Dispos., July 1, 2006; 34(7): 1190 - 1197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Ruiz, S. S. M. Villanueva, M. G. Luquita, M. Vore, A. D. Mottino, and V. A. Catania ETHYNYLESTRADIOL INCREASES EXPRESSION AND ACTIVITY OF RAT LIVER MRP3 Drug Metab. Dispos., June 1, 2006; 34(6): 1030 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dallas, D. S. Miller, and R. Bendayan Multidrug resistance-associated proteins: expression and function in the central nervous system. Pharmacol. Rev., June 1, 2006; 58(2): 140 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Couture, J. A. Nash, and J. Turgeon The ATP-Binding Cassette Transporters and Their Implication in Drug Disposition: A Special Look at the Heart. Pharmacol. Rev., June 1, 2006; 58(2): 244 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nishiya, H. Kataoka, K. Mori, M. Goto, T. Sugawara, and K. Furuhama Tienilic Acid Enhances Hyperbilirubinemia in Eisai Hyperbilirubinuria Rats through Hepatic Multidrug Resistance-Associated Protein 3 and Heme Oxygenase-1 Induction Toxicol. Sci., June 1, 2006; 91(2): 651 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Chandra, B. M. Johnson, P. Zhang, G. M. Pollack, and K. L. R. Brouwer MODULATION OF HEPATIC CANALICULAR OR BASOLATERAL TRANSPORT PROTEINS ALTERS HEPATOBILIARY DISPOSITION OF A MODEL ORGANIC ANION IN THE ISOLATED PERFUSED RAT LIVER Drug Metab. Dispos., August 1, 2005; 33(8): 1238 - 1243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Maher, A. L. Slitt, N. J. Cherrington, X. Cheng, and C. D. Klaassen TISSUE DISTRIBUTION AND HEPATIC AND RENAL ONTOGENY OF THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP) FAMILY IN MICE Drug Metab. Dispos., July 1, 2005; 33(7): 947 - 955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Maher, X. Cheng, A. L. Slitt, M. Z. Dieter, and C. D. Klaassen INDUCTION OF THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN FAMILY OF TRANSPORTERS BY CHEMICAL ACTIVATORS OF RECEPTOR-MEDIATED PATHWAYS IN MOUSE LIVER Drug Metab. Dispos., July 1, 2005; 33(7): 956 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Augustine, R. J. Markelewicz Jr., K. Boekelheide, and N. J. Cherrington XENOBIOTIC AND ENDOBIOTIC TRANSPORTER MRNA EXPRESSION IN THE BLOOD-TESTIS BARRIER Drug Metab. Dispos., January 1, 2005; 33(1): 182 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. St-Pierre, T. Stallmach, A. Freimoser Grundschober, J.-F. Dufour, M. A. Serrano, J. J. G. Marin, Y. Sugiyama, and P. J. Meier Temporal expression profiles of organic anion transport proteins in placenta and fetal liver of the rat Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2004; 287(6): R1505 - R1516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-S. Kim, S. Wang, Z. Shen, C. J. Kochansky, J. R. Strauss, R. B. Franklin, and S. H. Vincent DIFFERENCES IN THE PHARMACOKINETICS OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR AGONISTS IN GENETICALLY OBESE ZUCKER AND SPRAGUE-DAWLEY RATS: IMPLICATIONS OF DECREASED GLUCURONIDATION IN OBESE ZUCKER RATS Drug Metab. Dispos., September 1, 2004; 32(9): 909 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Cherrington, A. L. Slitt, N. Li, and C. D. Klaassen LIPOPOLYSACCHARIDE-MEDIATED REGULATION OF HEPATIC TRANSPORTER mRNA LEVELS IN RATS Drug Metab. Dispos., July 1, 2004; 32(7): 734 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Wright and W. H. Dantzler Molecular and Cellular Physiology of Renal Organic Cation and Anion Transport Physiol Rev, July 1, 2004; 84(3): 987 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. H. M. Heijne, A. L. Slitt, P. J. van Bladeren, J. P. Groten, C. D. Klaassen, R. H. Stierum, and B. van Ommen Bromobenzene-Induced Hepatotoxicity at the Transcriptome Level Toxicol. Sci., June 1, 2004; 79(2): 411 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Hartley, X. Dai, Y. D. He, E. J. Carlini, B. Wang, S.-e. W. Huskey, R. G. Ulrich, T. H. Rushmore, R. Evers, and D. C. Evans Activators of the Rat Pregnane X Receptor Differentially Modulate Hepatic and Intestinal Gene Expression Mol. Pharmacol., May 1, 2004; 65(5): 1159 - 1171. [Abstract] [Full Text]
|
|
|
|
|
|
C. Handschin and U. A. Meyer Induction of Drug Metabolism: The Role of Nuclear Receptors Pharmacol. Rev., December 1, 2003; 55(4): 649 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Cherrington, A. L. Slitt, J. M. Maher, X.-X. Zhang, J. Zhang, W. Huang, Y.-J. Y. Wan, D. D. Moore, and C. D. Klaassen INDUCTION OF MULTIDRUG RESISTANCE PROTEIN 3 (MRP3) IN VIVO IS INDEPENDENT OF CONSTITUTIVE ANDROSTANE RECEPTOR Drug Metab. Dispos., November 1, 2003; 31(11): 1315 - 1319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Choudhuri, N. J. Cherrington, N. Li, and C. D. Klaassen CONSTITUTIVE EXPRESSION OF VARIOUS XENOBIOTIC AND ENDOBIOTIC TRANSPORTER mRNAs IN THE CHOROID PLEXUS OF RATS Drug Metab. Dispos., November 1, 2003; 31(11): 1337 - 1345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Slitt, N. J. Cherrington, J. M. Maher, and C. D. Klaassen INDUCTION OF MULTIDRUG RESISTANCE PROTEIN 3 IN RAT LIVER IS ASSOCIATED WITH ALTERED VECTORIAL EXCRETION OF ACETAMINOPHEN METABOLITES Drug Metab. Dispos., September 1, 2003; 31(9): 1176 - 1186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Potschka, M. Fedrowitz, and W. Loscher Multidrug Resistance Protein MRP2 Contributes to Blood-Brain Barrier Function and Restricts Antiepileptic Drug Activity J. Pharmacol. Exp. Ther., July 1, 2003; 306(1): 124 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Rosenfeld, R. Vargas Jr., W. Xie, and R. M. Evans Genetic Profiling Defines the Xenobiotic Gene Network Controlled by the Nuclear Receptor Pregnane X Receptor Mol. Endocrinol., July 1, 2003; 17(7): 1268 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Walter, C. Ullmann, D. Thummler, and W. Siegmund INFLUENCE OF PROPIVERINE ON HEPATIC MICROSOMAL CYTOCHROME P450 ENZYMES IN MALE RATS Drug Metab. Dispos., June 1, 2003; 31(6): 714 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wang, D. P. Hartley, S. L. Ciccotto, S. H. Vincent, R. B. Franklin, and M.-S. Kim INDUCTION OF HEPATIC PHASE II DRUG-METABOLIZING ENZYMES BY 1,7-PHENANTHROLINE IN RATS IS ACCOMPANIED BY INDUCTION OF MRP3 Drug Metab. Dispos., June 1, 2003; 31(6): 773 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Staudinger, A. Madan, K. M. Carol, and A. Parkinson Regulation of Drug Transporter Gene Expression by Nuclear Receptors Drug Metab. Dispos., May 1, 2003; 31(5): 523 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Trauner and J. L. Boyer Bile Salt Transporters: Molecular Characterization, Function, and Regulation Physiol Rev, April 1, 2003; 83(2): 633 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Leazer and C. D. Klaassen The Presence of Xenobiotic Transporters in Rat Placenta Drug Metab. Dispos., February 1, 2003; 31(2): 153 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Oleschuk, R. G. Deeley, and S. P. C. Cole Substitution of Trp1242 of TM17 alters substrate specificity of human multidrug resistance protein 3 Am J Physiol Gastrointest Liver Physiol, February 1, 2003; 284(2): G280 - G289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Gerk and M. Vore Regulation of Expression of the Multidrug Resistance-Associated Protein 2 (MRP2) and Its Role in Drug Disposition J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 407 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Brady, N. J. Cherrington, D. P. Hartley, S. C. Buist, N. Li, and C. D. Klaassen Tissue Distribution and Chemical Induction of Multiple Drug Resistance Genes in Rats Drug Metab. Dispos., July 1, 2002; 30(7): 838 - 844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Johnson and C. D. Klaassen Regulation of Rat Multidrug Resistance Protein 2 by Classes of Prototypical Microsomal Enzyme Inducers That Activate Distinct Transcription Pathways Toxicol. Sci., June 1, 2002; 67(2): 182 - 189. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
