Choudhuri Supratim, Cherrington Nathan J, Li Ning, Klaassen Curtis D
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160-7417, USA.
Drug Metab Dispos. 2003 Nov;31(11):1337-45. doi: 10.1124/dmd.31.11.1337.
The aim of this study was to quantitatively determine the constitutive expression levels of various transporter mRNAs in rat choroid plexus. To provide a reference for the relative expression levels, the expression of various transporter mRNAs in choroid plexus were compared with that in liver, kidney, and ileum. The mRNA levels of multidrug resistance protein (Mrp)1, 2, 3, 4, 5, and 6; multidrug resistance (Mdr)1a, 1b, and 2; organic anion transporting polypeptide (Oatp)1, 2, 3, 4, 5, 9, 12, and Oat-K (1/2); organic anion transporter (Oat)1, 2, and 3; organic cation transporter (Oct)1, 2, 3, N1, and N2; bile acid transporters sodium taurocholate cotransporting polypeptide (Ntcp), bile salt excretory protein (Bsep), and ileal bile acid transporter (Ibat); divalent metal transporter 1 (DMT1), Menke's and Wilson's metal transporters; equilibrative nucleotide transporters (Ent) 1 and 2, and constitutive nucleotide transporters (Cnt)1 and 2; peptide transporters (Pept)1 and 2; as well as ATP-binding cassette (Abc)G5 and 8 were measured in choroid plexus by the branched DNA signal amplification method. Mrp1, 4, and 5, Oatp3, Menke's transporter, DMT1, Ent1, and Pept2 mRNAs were expressed in choroid plexus at higher levels than in liver, kidney, or ileum. OctN1 and N2, Oatp2, Oat2 and 3, and Cnt1 and 2 mRNAs expressions were detectable in choroid plexus, but the levels were lower compared with that in liver, kidney, or ileum. The remaining transporters [Mrp2, Mrp3, Oct1, Oct2, Oatp1, Oatp4, Oatp5, Oatp12, Oat-K (1/2), Ntcp, Bsep, Ibat, Mdr1a, Mdr1b, Mdr2, Oat1, Ent2, Pept1, AbcG5, AbcG8] were expressed at very low levels in choroid plexus. The constitutive expression levels of different transporters in choroid plexus may provide an insight into the range of xenobiotics that can potentially be transported by the choroid plexus, thereby providing a means of xenobiotic detoxification in the brain.
本研究的目的是定量测定大鼠脉络丛中各种转运蛋白mRNA的组成性表达水平。为了给相对表达水平提供参考，将脉络丛中各种转运蛋白mRNA的表达与肝脏、肾脏和回肠中的表达进行了比较。采用分支DNA信号放大法测定了脉络丛中多药耐药蛋白（Mrp）1、2、3、4、5和6；多药耐药（Mdr）1a、1b和2；有机阴离子转运多肽（Oatp）1、2、3、4、5、9、12和Oat-K（1/2）；有机阴离子转运体（Oat）1、2和3；有机阳离子转运体（Oct）1、2、3、N1和N2；胆汁酸转运体牛磺胆酸钠共转运多肽（Ntcp）、胆汁盐排泄蛋白（Bsep）和回肠胆汁酸转运体（Ibat）；二价金属转运体1（DMT1）、门克斯病和威尔逊病金属转运体；平衡型核苷酸转运体（Ent）1和2以及组成型核苷酸转运体（Cnt）1和2；肽转运体（Pept）1和2；以及ATP结合盒（Abc）G5和8的mRNA水平。Mrp1、4和5、Oatp3、门克斯病转运体、DMT1、Ent1和Pept2的mRNA在脉络丛中的表达水平高于肝脏、肾脏或回肠。OctN1和N2、Oatp2、Oat2和3以及Cnt1和2的mRNA表达在脉络丛中可检测到，但与肝脏、肾脏或回肠相比水平较低。其余转运蛋白[Mrp2、Mrp3、Oct1、Oct2、Oatp1、Oatp4、Oatp5、Oatp12、Oat-K（1/2）、Ntcp、Bsep、Ibat、Mdr1a、Mdr1b、Mdr2、Oat1、Ent2、Pept1、AbcG5、AbcG8]在脉络丛中的表达水平非常低。脉络丛中不同转运蛋白的组成性表达水平可能有助于深入了解脉络丛可能转运的外源性物质范围，从而为大脑中的外源性物质解毒提供一种方式。
