Lu Hong, Chen Chuan, Klaassen Curtis
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160-7417, USA.
Drug Metab Dispos. 2004 Dec;32(12):1455-61. doi: 10.1124/dmd.104.001123. Epub 2004 Sep 15.
Concentrative nucleoside transporters (Cnts) and equilibrative nucleoside transporters (Ents) have essential physiological functions and are important in disposition of anticancer and antiviral nucleoside analogs. Information on tissue distribution of Cnts and Ents in rodents is sparse. Thus, the present study aimed to determine the distribution of Cnt1-3 and Ent1-3 transcripts in 19 tissues of Sprague-Dawley rats and C57BL/6 mice of both genders. These six transcripts were quantified using the branched DNA signal amplification assay. Cnt1 transcripts were highest in small intestine, followed by kidney and testes, with similar expression in both species. Cnt2 mRNA was expressed highest in the small intestine of both rats and mice, intermediate in liver of rats but not in mice, and lower in thymus and spleen of both species. Cnt3 mRNA has marked species differences, with the highest expression in lung of rats but uterus of mice. Ent1 mRNA was most highly expressed in testes and lung of both species. Ent1 mRNA was highly expressed in liver and pituitary of mice, but not in rats. Ent2 mRNA was highly expressed in testes and brain of both species. Ent3 mRNA was highest in kidney, followed by testes, in both species. Significant gender differences were observed in kidney (mouse) and heart (rat). These studies demonstrate that in general, tissue distribution of Cnt and Ent is similar in rats and mice. However, a few important species and gender differences do exist, which could be responsible for related differences in efficacy and toxicity of substrates for these transporters.
浓缩型核苷转运体(Cnts)和平衡型核苷转运体(Ents)具有重要的生理功能,在抗癌和抗病毒核苷类似物的处置中发挥重要作用。关于啮齿动物中Cnts和Ents的组织分布信息较少。因此,本研究旨在确定Cnt1 - 3和Ent1 - 3转录本在不同性别的Sprague - Dawley大鼠和C57BL / 6小鼠的19种组织中的分布。使用分支DNA信号放大测定法对这六种转录本进行定量。Cnt1转录本在小肠中最高,其次是肾脏和睾丸,两种物种中的表达相似。Cnt2 mRNA在大鼠和小鼠的小肠中表达最高,在大鼠肝脏中表达中等但在小鼠肝脏中不表达,在两种物种的胸腺和脾脏中表达较低。Cnt3 mRNA存在明显的物种差异,在大鼠肺中表达最高但在小鼠子宫中表达最高。Ent1 mRNA在两种物种的睾丸和肺中表达最高。Ent1 mRNA在小鼠肝脏和垂体中高表达,但在大鼠中不表达。Ent2 mRNA在两种物种的睾丸和脑中高表达。Ent3 mRNA在两种物种的肾脏中最高,其次是睾丸。在肾脏(小鼠)和心脏(大鼠)中观察到显著的性别差异。这些研究表明,一般而言,大鼠和小鼠中Cnt和Ent的组织分布相似。然而,确实存在一些重要的物种和性别差异,这可能是这些转运体底物在疗效和毒性方面相关差异的原因。