Alnouti Yazen, Petrick Jay S, 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. 2006 Mar;34(3):477-82. doi: 10.1124/dmd.105.006932. Epub 2005 Dec 28.
Organic cation transporters (Octs) play an important role in transporting cationic xeno- and endobiotics across biological membranes. Little is known about Octs in mice; therefore, the tissue distribution and developmental changes in the mRNA expression of Octs in mice were quantified. Oct1, Oct2, Oct3, Octn1, Octn2, and Octn3 mRNA expression was quantified in 14 tissues from male and female mice using the branched DNA signal amplification assay. Oct1 mRNA expression was highest in kidney, followed by liver. Oct2 mRNA was almost exclusively expressed in kidney, with male mice having twice that in female mice. The higher expression of Oct2 in male mice is due to testosterone. Oct3 mRNA was most highly expressed in placenta, ovary, and uterus, but was expressed at low levels in most tissues. Octn1 and Octn2 mRNA expression was similar, with the highest levels in kidney followed by small intestine. Octn3 mRNA was almost exclusively expressed in testes. The developmental expression of Oct1, Oct2, Octn1, and Octn2 mRNA in kidneys as well as Oct1 in liver was determined in young mice. Ontogenic expression data indicate that each of the Octs approached adult expression levels by about 3 weeks of age. The gender difference in Oct mRNA expression did not become apparent until day 30 after birth. The differences in tissue distribution of the Octs may play an important role in drug disposition to various tissues. Furthermore, low expression of the Octs in young animals may affect the pharmacokinetic behavior of drugs compared with that in adults.
有机阳离子转运体（Octs）在阳离子外源生物和内源性生物活性物质跨生物膜转运过程中发挥着重要作用。目前对小鼠体内的Octs了解甚少；因此，对小鼠Octs mRNA表达的组织分布及发育变化进行了定量分析。采用分支DNA信号放大检测法对雄性和雌性小鼠14种组织中的Oct1、Oct2、Oct3、Octn1、Octn2和Octn3 mRNA表达进行了定量分析。Oct1 mRNA在肾脏中表达最高，其次是肝脏。Oct2 mRNA几乎仅在肾脏中表达，雄性小鼠中的表达量是雌性小鼠的两倍。雄性小鼠中Oct2的高表达是由睾酮引起的。Oct3 mRNA在胎盘、卵巢和子宫中表达最高，但在大多数组织中表达水平较低。Octn1和Octn2 mRNA表达相似，在肾脏中表达水平最高，其次是小肠。Octn3 mRNA几乎仅在睾丸中表达。在幼鼠中测定了Oct1、Oct2、Octn1和Octn2 mRNA在肾脏中的发育表达以及Oct1在肝脏中的发育表达。个体发育表达数据表明，每种Octs在约3周龄时接近成年表达水平。Oct mRNA表达的性别差异直到出生后30天才变得明显。Octs在组织分布上的差异可能在药物向各种组织的处置过程中起重要作用。此外，与成年动物相比，幼龄动物中Octs的低表达可能会影响药物的药代动力学行为。
