Human placental monoamine transporters as targets for amphetamines
Human placental monoamine transporters as targets for amphetamines
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DOI：
10.1016/0002-9378(95)90427-1
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发表时间：
1995-12-01
影响因子：
9.8
通讯作者：
Ganapathy, V
中科院分区：
文献类型：
--
作者：
Ramamoorthy, JD;Ramamoorthy, S;Ganapathy, V
兴奋剂：已知在怀孕期间使用安非他明及其衍生物对怀孕结果有不良影响。这些影响至少部分是由于这些滥用药物造成的胎盘功能损害。我们假设，这两个单胺转运，即，5-羟色胺转运和去甲肾上腺素转运，这是在人类胎盘中表达的直接目标为these drugs.Study设计：苯丙胺和甲基苯丙胺与人类胎盘5-羟色胺和去甲肾上腺素转运的相互作用进行了检查。5-羟色胺转运体的活性通过从正常足月人胎盘和绒毛膜癌细胞中分离的面向母体的刷状缘膜囊泡中的5-羟色胺摄取来评估。多巴胺的摄取和nisoxetine结合在胎盘刷状缘膜vesicle.Results：安非他明和甲基苯丙胺是有效的抑制剂的5-羟色胺和去甲肾上腺素转运蛋白在人胎盘中表达的活性进行了评估。苯丙胺的抑制效力大于甲基苯丙胺。在每种情况下，S（+）非对映异构体比相应的R（-）非对映异构体更有效。去甲肾上腺素转运蛋白对这些药物抑制的敏感性至少比5-羟色胺转运蛋白高两个数量级。在已知的浓度发生在用户的血浆中，这些药物引起显着抑制的去甲肾上腺素transporter.CONCLUSIONS：结果表明，去甲肾上腺素转运体，并在较小程度上，5-羟色胺转运体的细胞靶向在人胎盘的滥用药物苯丙胺和甲基苯丙胺。
OBJECTIVES: The use of amphetamine and its derivatives during pregnancy is known to have adverse effects on the outcome of pregnancy. These effects are at least partly a result of impairment of placental function caused by these abusable drugs. We hypothesized that the two monoamine transporters, namely, the serotonin transporter and the norepinephrine transporter, that are expressed in the human placenta are direct targets for these drugs.STUDY DESIGN: The interaction of amphetamine and methamphetamine with human placental serotonin and norepinephrine transporters was examined. Activity of the serotonin transporter was assessed by serotonin uptake in both maternal-facing brush border membrane vesicles isolated from normal term human placentas and in JAR choriocarcinoma cells. Activity of the norepineprhine transporter was assessed by dopamine uptake and nisoxetine binding in placental brush border membrane vesicles.RESULTS: Amphetamine and methamphetamine are potent inhibitors of the serotonin and norepinephrine transporters expressed in the human placenta. The inhibitory potency of amphetamine is greater than that of methamphetamine. In each case, the S(+)diastereoisomer is more potent than the corresponding R(-)diastereoisomer. The sensitivity of the norepinephrine transporter to inhibition by these drugs is at least two orders of magnitude greater than that of the serotonin transporter. At concentrations known to occur in the plasma of users, these drugs cause a marked inhibition of the norepinephrine transporter.CONCLUSIONS: The results show that the norepinephrine transporter and, to a lesser extent, the serotonin transporter are cellular targets in the human placenta for the abusable drugs amphetamine and methamphetamine.