Characterization of an organic anion transport system in a placental cell line.
Characterization of an organic anion transport system in a placental cell line.
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胎盘细胞系中有机阴离子转运系统的表征。
DOI：
10.1152/ajpendo.00182.2003
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
You,Guofeng
中科院分区：
文献类型：
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作者：
Zhou,Fanfan;Tanaka,Kunihiko;Soares,MichaelJ;You,Guofeng
胎盘内的转运蛋白在营养物质和外源物质在母胎界面的分配中发挥着至关重要的作用。在大鼠胎盘细胞系 HRP-1（胎盘屏障的模型）的顶膜上发现了有机阴离子转运系统。 HRP-1细胞中3 H标记的有机阴离子雌酮硫酸盐的顶端摄取是饱和的(Km=4.67μM)、温度和Na+依赖性、Li+耐受性和pH敏感性。转运系统的底物特异性包括各种类固醇硫酸盐，例如β-雌二醇3,17-二硫酸盐、17β-雌二醇3-硫酸盐和脱氢表雄酮3-硫酸盐(DHEAS)，但不包括牛磺胆酸盐、对氨基马尿酸(PAH)和四乙铵。将 HRP-1 细胞与 8-bromo-cAMP（一种 cAMP 类似物）和毛喉素（一种腺苷酸环化酶激活剂）预孵育可剧烈刺激顶端转运活性。 IBMX（一种磷酸二酯酶抑制剂）的存在进一步增强了这种刺激。这些数据共同表明，HRP-1 细胞的顶膜表达受细胞 cAMP 水平调节的有机阴离子转运系统。该转运系统似乎不同于已知的牛磺胆酸盐转运有机阴离子转运多肽和PAH转运有机阴离子转运蛋白，这两者也介导硫酸雌酮和DHEAS的转运。
Transporters within the placenta play a crucial role in the distribution of nutrients and xenobiotics across the maternal-fetal interface. An organic anion transport system was identified on the apical membrane of the rat placenta cell line HRP-1, a model for the placenta barrier. The apical uptake of3H-labeled organic anion estrone sulfate in HRP-1 cells was saturable (Km= 4.67 μM), temperature and Na+dependent, Li+tolerant, and pH sensitive. The substrate specificity of the transport system includes various steroid sulfates, such as β-estradiol 3,17-disulfate, 17β-estradiol 3-sulfate, and dehydroepiandrosterone 3-sulfate (DHEAS) but does not include taurocholate,p-aminohippuric acid (PAH), and tetraethylammonium. Preincubation of HRP-1 cells with 8-bromo-cAMP (a cAMP analog) and forskolin (an adenylyl cyclase activator) acutely stimulated the apical transport activity. This stimulation was further enhanced in the presence of IBMX (a phosphodiesterase inhibitor). Together these data show that the apical membrane of HRP-1 cells expresses an organic anion transport system that is regulated by cellular cAMP levels. This transport system appears to be different from the known taurocholate-transporting organic anion-transporting polypeptides and PAH-transporting organic anion transporters, both of which also mediate the transport of estrone sulfate and DHEAS.