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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Multiple Drug Transporters Contribute to the Placental Transfer of Emtricitabine
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Multiple Drug Transporters Contribute to the Placental Transfer of Emtricitabine

机译：多种药物运输器有助于胎盘植物转移

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摘要

Emtricitabine (FTC) is a first-line antiviral drug recommended for the treatment of AIDS during pregnancy. We hypothesized that transporters located in the placenta contribute to FTC transfer across the blood-placenta barrier. BeWo cells, cell models with stable or transient expression of transporter genes, primary human trophoblast cells (PHTCs), and small interfering RNAs (siRNAs) were applied to demonstrate which transporters were involved. FTC accumulation in BeWo cells was reduced markedly by inhibitors of equilibrative nucleoside transporters (ENTs), concentrative nucleoside transporters (CNTs), organic cation transporters (OCTs), and organic cation/carnitine transporter 1 (OCTN1) and increased by inhibitors of breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs). ENT1, CNT1, OCTN1, MRP1/2/3, and BCRP, but not ENT2, CNT3, OCTN2, or multidrug resistance protein 1 (MDR1), were found to transport FTC. FTC accumulation in PHTCs was decreased significantly by inhibitors of ENTs and OCTN1. These results suggest that ENT1, CNT1, and OCTN1 probably contribute to FTC uptake from maternal circulation to trophoblasts and that ENT1. CNT1, and MRP1 are likely involved in FTC transport between trophoblasts and fetal blood, whereas BCRP and MRP1/2/3 facilitate FTC transport from trophoblasts to maternal circulation. Coexistence of tenofovir or efavirenz with FTC in the cell medium did not influence FTC accumulation in BeWo cells or PHTCs.
机译：Emtricitabine（FTC）是推荐在怀孕期间治疗艾滋病的一线抗病毒药物。我们假设位于胎盘的运输工具有助于穿过血液胎盘屏障的FTC转移。 Bewo细胞，具有稳定或瞬态表达的转运蛋白基因，原发性人滋养细胞（PHTC）和小干扰RNA（siRNA）的细胞模型被应用于表明涉及的转运蛋白。通过平衡核苷转运蛋白（ENTES），浓缩核苷转运蛋白（CNT），有机阳离子转运蛋白（OCT）和有机阳离子/肉碱转运蛋白1（OCTN1）的抑制剂明显减少了Bewo细胞中的累积，并通过乳腺癌抗性的抑制剂增加蛋白质（BCRP）和多药抗性相关蛋白（MRPS）。发现ENT1，CNT1，OCTN1，MRP1 / 2/3和BCRP，但不是ENT2，CNT3，OCTN2或多药抗性蛋白1（MDR1）运输FTC。抑制剂和OctN1的抑制剂，PHTCS中的FTC积累显着降低。这些结果表明ENT1，CNT1和OCTN1可能有助于FTC从母体循环到滋养板和ent1的FTC摄取。 CNT1和MRP1可能参与滋养细胞和胎儿之间的FTC传输，而BCRP和MRP1 / 2/3促进来自滋养管的FTC运输到母体血液。细胞培养基中替诺福韦或EFAVIRENZ与FTC的共存并未影响Bewo细胞或pHTC中的FTC积累。

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  • 作者

    Zeng Qingquan; Bai Mengru; Li Cui; Lu Shuanghui; Ma Zhiyuan; Zhao Yunchun; Zhou Hui; Jiang Huidi; Sun Dongli; Zheng Caihong;

  • 作者单位

    Zhejiang Univ Womens Hosp Sch Med Hangzhou Zhejiang Peoples R China;

    Zhejiang Univ Coll Pharmaceut Sci Hangzhou Zhejiang Peoples R China;

    Zhejiang Univ Coll Pharmaceut Sci Hangzhou Zhejiang Peoples R China;

    Zhejiang Univ Coll Pharmaceut Sci Hangzhou Zhejiang Peoples R China;

    Zhejiang Univ Coll Pharmaceut Sci Hangzhou Zhejiang Peoples R China;

    Zhejiang Univ Womens Hosp Sch Med Hangzhou Zhejiang Peoples R China;

    Zhejiang Univ Coll Pharmaceut Sci Hangzhou Zhejiang Peoples R China;

    Zhejiang Univ Coll Pharmaceut Sci Hangzhou Zhejiang Peoples R China;

    Zhejiang Univ Womens Hosp Sch Med Hangzhou Zhejiang Peoples R China;

    Zhejiang Univ Womens Hosp Sch Med Hangzhou Zhejiang Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 治疗学;
  • 关键词

    emtricitabine; placenta; transporters; BeWo;

    机译：Emtricitabine;胎盘;运输器;Bewo;

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