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Rapid CommunicationSpecial Section on Drug Metabolizing Enzymes and Transporters in Pregnancy

Down-Regulation of Brush Border Efflux Transporter Expression in the Kidneys of Pregnant Mice

Lindsay L. Yacovino, Christopher J. Gibson and Lauren M. Aleksunes
Drug Metabolism and Disposition February 2013, 41 (2) 320-325; DOI: https://doi.org/10.1124/dmd.112.047092
Lindsay L. Yacovino
Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy (L.L.Y., C.J.G., L.M.A.), and Environmental and Occupational Health Sciences Institute, a Joint Institute of Robert Wood Johnson Medical School and Rutgers University, Piscataway, New Jersey (L.M.A.)
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Christopher J. Gibson
Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy (L.L.Y., C.J.G., L.M.A.), and Environmental and Occupational Health Sciences Institute, a Joint Institute of Robert Wood Johnson Medical School and Rutgers University, Piscataway, New Jersey (L.M.A.)
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Lauren M. Aleksunes
Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy (L.L.Y., C.J.G., L.M.A.), and Environmental and Occupational Health Sciences Institute, a Joint Institute of Robert Wood Johnson Medical School and Rutgers University, Piscataway, New Jersey (L.M.A.)
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Abstract

Pregnancy increases the urinary excretion of chemicals in women and rodents. It is unknown whether the enhanced clearance of drugs during pregnancy involves changes in the expression of transporters that mediate chemical secretion and reabsorption. The purpose of this study was to quantify the mRNA and protein expression of efflux transporters in kidneys from virgin and pregnant mice on gestational days 7, 11, 14, and 17 and postnatal days 1, 15, and 30 with use of quantitative polymerase chain reaction, Western blot, and immunofluorescence. Multidrug resistance protein (Mdr) 1b mRNA, multidrug resistance-associated protein (Mrp) 4 mRNA, and protein levels decreased significantly by 25–75% throughout pregnancy and lactation. Similarly, Mrp2 and multidrug and toxin extrusion transporter (Mate) 1 mRNA expression were down-regulated 20–40% during mid to late gestation but returned to control levels by postnatal day 15. In contrast, Mrp3 mRNA and protein increased 225% and 31%, respectively, at gestational day 14. Coordinated down-regulation of brush border transporters Mate1, Mrp2, and Mrp4 and up-regulation of the basolateral Mrp3 transporter would reduce chemical secretion into urine.

Footnotes

  • This work was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant DK080774], and the National Institutes of Health National Institute of Environmental Health Sciences [Grants ES020522, ES005022, and ES007148].

  • ↵Embedded ImageThis article has supplemental material available at dmd.aspetjournals.org.

  • dx.doi.org/10.1124/dmd.112.047092.

  • Received June 6, 2012.
  • Accepted August 14, 2012.
  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 41 (2)
Drug Metabolism and Disposition
Vol. 41, Issue 2
1 Feb 2013
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Rapid CommunicationSpecial Section on Drug Metabolizing Enzymes and Transporters in Pregnancy

Renal Transporters in Pregnant Mice

Lindsay L. Yacovino, Christopher J. Gibson and Lauren M. Aleksunes
Drug Metabolism and Disposition February 1, 2013, 41 (2) 320-325; DOI: https://doi.org/10.1124/dmd.112.047092

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Rapid CommunicationSpecial Section on Drug Metabolizing Enzymes and Transporters in Pregnancy

Renal Transporters in Pregnant Mice

Lindsay L. Yacovino, Christopher J. Gibson and Lauren M. Aleksunes
Drug Metabolism and Disposition February 1, 2013, 41 (2) 320-325; DOI: https://doi.org/10.1124/dmd.112.047092
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