Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ, USA.
Drug Metab Dispos. 2013 Feb;41(2):320-5. doi: 10.1124/dmd.112.047092. Epub 2012 Aug 15.
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.
妊娠会增加女性和啮齿动物尿液中化学物质的排泄量。目前尚不清楚怀孕期间药物清除率的增加是否涉及介导化学物质分泌和重吸收的转运体表达的变化。本研究的目的是使用定量聚合酶链反应、Western blot 和免疫荧光定量分析妊娠 7、11、14 和 17 天及产后 1、15 和 30 天的处女和妊娠小鼠肾脏中流出转运体的 mRNA 和蛋白表达。多药耐药蛋白 1b (Mdr) 1b mRNA、多药耐药相关蛋白 4 (Mrp) 4 mRNA 和蛋白水平在整个妊娠和哺乳期显著下降 25-75%。同样，Mrp2 和多药和毒素外排转运蛋白 (Mate) 1 mRNA 表达在妊娠中期至晚期下调 20-40%，但在产后第 15 天恢复到对照水平。相比之下，Mrp3 mRNA 和蛋白分别增加了 225%和 31%，在妊娠第 14 天达到高峰。刷状缘转运体 Mate1、Mrp2 和 Mrp4 的协调下调和基底外侧 Mrp3 转运体的上调会减少化学物质分泌到尿液中。
