Expression of a cocaine-sensitive norepinephrine transporter in the human placental syncytiotrophoblast.
Expression of a cocaine-sensitive norepinephrine transporter in the human placental syncytiotrophoblast.
复制标题
可卡因敏感的去甲肾上腺素转运蛋白在人胎盘合体滋养层中的表达。
DOI：
10.1021/bi00056a021
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发表时间：
1993
期刊：
影响因子：
2.9
通讯作者：
Ganapathy,V
中科院分区：
文献类型：
--
作者：
Ramamoorthy,S;Prasad,PD;Kulanthaivel,P;Leibach,FH;Blakely,RD;Ganapathy,V
1992年11月23日收到的修订版Mandarin pt摘要：发现从正常足月人胎盘中分离的面向母体的刷状缘膜囊泡在存在向内定向的NaCl梯度的情况下以集中的方式蓄积去甲肾上腺素。Na+和Cl-都是最大吸收的必需品。NaCl依赖性去甲肾上腺素摄取进一步刺激的存在下，K+或酸性pH值的囊内介质。的吸收过程是产电的，被刺激的内部负膜电位，并观察到这种特性的情况下，以及在存在的K+囊泡内。动力学分析表明，去甲肾上腺素的表观米氏常数为104±5 nM，每转运一个去甲肾上腺素分子，涉及一个Na+和一个CT。摄取过程中表现出更高的亲和力多巴胺比去甲肾上腺素，但有低亲和力的阿托宁和组胺。诺米芬辛、地昔帕明、丙咪嗪和可卡因非常有效地抑制去甲肾上腺素的摄取，但安非他酮和GBR 12909的抑制效果要差得多。以人（SK-N-SH细胞）去甲肾上腺素转运蛋白的cDNA作为探针的北方印迹分析显示，人胎盘含有两种大小为5.8和3.6 kb的mRNA，它们与探针杂交。人胎盘绒毛膜癌细胞不能以NaCl依赖的方式积累去甲肾上腺素。在北方印迹中，这些细胞也不含与去甲肾上腺素cDNA探针杂交的mRNA。它的结论是，人类胎盘合胞体滋养层表达可卡因敏感的去甲肾上腺素转运蛋白，这些研究结果可能是直接相关的和重要的临床并发症的母亲在怀孕期间滥用可卡因。
Revised Manuscript Received November 23, 1992 abstract: Maternal-facing brush border membrane vesicles isolated from normal term human placentas were found to accumulate norepinephrine in a concentrative manner in the presence of an inwardly directed NaCl gradient. Both Na+ and Cl-were obligatory for maximal uptake. The NaCl-dependent norepinephrine uptake was further stimulated by the presence of K+ or an acidic pH in the intravesicular medium. The uptake process was electrogenic, being stimulated by an inside-negative membrane potential, and this characteristic was observed in the absence as well as in the presence of K+ inside the vesicles. Kinetic analyses revealed that one Na+ and one CT were involved per transport of one norepinephrine molecule.The apparent Michaelis-Menten constant for norepinephrine was 104±5 nM. The uptake process exhibited higher affinity for dopamine than for norepinephrine but had low affinity for serotoninand histamine. The uptake of norepinephrine was inhibited very effectively by nomifensine, desipramine, imipramine, and cocaine, but much less effectively by bupropion and GBR 12909. Northern blot analysis with the cDNA of the human (SK-N-SH cell) norepinephrine transporter as the probe revealed that the human placenta contained two mRNAs, 5.8 and 3.6 kb in size, which hybridized to the probe. The JAR human placental choriocarcinoma cells were found unable to accumulate norepinephrine in a NaCl-dependent manner. These cells were also found not to contain mRNAs which hybridized to the norepinephrine cDNA probe in northern blot. It is concluded that the human placental syncytiotrophoblast expresses a cocaine-sensitive norepinephrine transporter and that these findings may be directly relevant and important to the clinical complications of maternal cocaine abuse during pregnancy.