Abstract：
3\'-Azido-3\'-deoxythymidine (AZT), an antiretroviral drug, is often adopted in the therapy for human immunodeficiency virus (HIV) infection, and the characteristics of AZT transport at the blood-testis barrier (BTB) were investigated in this study. In the integration plot analysis that evaluates the transport activity in vivo, the apparent influx clearance of [3H]AZT was significantly greater than that of [14C]D-mannitol, a non-permeable paracellular transport marker. In the uptake study in vitro with TM4 cells derived from mouse Sertoli cells, [3H]AZT uptake exhibited a time- and concentration-dependent manner, of which Km and Vmax values being 20.3 µM and 102 pmol/(min·mg protein), respectively. In the inhibition analysis, [3H]AZT uptake was not affected by extracellular inorganics and some substrates of transporters putatively involved in AZT transport. In the further inhibition analyses to elucidate the characteristics of AZT transport, [3H]AZT uptake was strongly reduced in the presence of several nucleosides, that are categorized as 2\'-deoxynucleosides with pyrimidine, whereas little effect on [3H]AZT uptake was exhibited in the presence of other nucleosides, nucleobases, and antiretrovirals. These results suggest the influx transport of AZT from the circulating blood to the testis, and the involvement of carrier-mediated process at the BTB, which selectively recognizes 2\'-deoxynucleosides with a pyrimidine base.
摘要：
3\'-叠氮基-3\'-脱氧胸苷（AZT），一种抗逆转录病毒药物，通常用于人类免疫缺陷病毒（HIV）感染的治疗中，研究了AZT在血睾丸屏障（BTB）的转运特征。在评估体内转运活性的整合图分析中，[3H]AZT的表观流入清除率明显大于[14C]D-甘露醇，一种不可渗透的细胞旁转运标记。在来自小鼠支持细胞的TM4细胞的体外摄取研究中，[3H]AZT摄取表现出时间和浓度依赖性，其中Km和Vmax值为20.3µM和102pmol/（min·mg蛋白质），分别。在抑制分析中，[3H]AZT摄取不受细胞外无机物的影响，转运蛋白的某些底物可能参与AZT转运。在进一步的抑制分析中，以阐明AZT转运的特征，[3H]AZT吸收在几种核苷的存在下强烈降低，被归类为带有嘧啶的2'-脱氧核苷，而在其他核苷的存在下，对[3H]AZT吸收的影响很小，核碱基,和抗逆转录病毒药物。这些结果表明AZT从循环血液到睾丸的内流运输，以及BTB中载体介导的过程的参与，用嘧啶碱基选择性识别2'-脱氧核苷。
