Relationship between [125I]RTI-55-labeled cocaine binding sites and the serotonin transporter in rat placenta.
Relationship between [125I]RTI-55-labeled cocaine binding sites and the serotonin transporter in rat placenta.
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[125I]RTI-55 标记的可卡因结合位点与大鼠胎盘中血清素转运蛋白之间的关系。
DOI：
10.1152/ajpcell.1998.275.6.c1621
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Meyer,JS
中科院分区：
文献类型：
--
作者：
Shearman,LP;McReynolds,AM;Zhou,FC;Meyer,JS
我们用[125 I]RTI-55研究了大鼠胎盘中可卡因样结合位点的特征。[3 H]帕罗西汀结合和5-羟色胺（5-HT）和5-HT转运蛋白的免疫细胞化学染色也用于获得大鼠胎盘5-HT摄取的证据。[125 I]RTI-55饱和度分析与膜从正常妊娠第20天胎盘产生曲线Scatchard图，分为高和低亲和力成分（平均解离常数分别为0.29和7.9 nM）。各种单胺摄取抑制剂的药物竞争研究产生了复杂的多相位移曲线，尽管选择性5-HT摄取抑制剂西酞普兰的结果表明，5-HT转运蛋白是胎盘高亲和力[125 I]RTI-55结合的重要组成部分。此外，[3 H]帕罗西汀结合实验和整个胎盘中存在的5-HT和5-HT转运蛋白的免疫反应性支持了大鼠胎盘5-HT摄取系统的存在。两种抗体的免疫染色在交界区最强烈，而[125 I]RTI-55结合位点的密度在胎盘迷路中更大。这种差异可能是由于[125 I]RTI-55似乎标记了除5-HT转运蛋白外的其他细胞组分。可卡因和抗抑郁药敏感的5-HT转运体在胎盘中的存在对这些化合物对妊娠和胎儿发育的可能影响具有重要意义。
We investigated the characteristics of cocainelike binding sites in rat placenta using [125I]RTI-55. [3H]paroxetine binding and immunocytochemical staining for serotonin [5-hydroxytryptamine (5-HT)] and for the 5-HT transporter were also used to obtain evidence for rat placental 5-HT uptake. [125I]RTI-55 saturation analyses with membranes from normal gestational day 20 placentas yielded curvilinear Scatchard plots that were resolved into high- and low-affinity components (mean dissociation constants of 0.29 and 7.9 nM, respectively). Drug competition studies with various monoamine uptake inhibitors gave rise to complex multiphasic displacement curves, although the results obtained with the selective 5-HT uptake inhibitor citalopram suggest that the 5-HT transporter is an important component of placental high-affinity [125I]RTI-55 binding. The presence of a rat placental 5-HT uptake system was additionally supported by the [3H]paroxetine binding experiments and by the presence throughout the placenta of immunoreactivity for 5-HT and the 5-HT transporter. Immunostaining with both antibodies was most intense in the junctional zone, whereas the density of [125I]RTI-55 binding sites was greater in the placental labyrinth. This discrepancy may be due to the fact that [125I]RTI-55 appears to be labeling additional cellular components besides the 5-HT transporter. The presence of cocaine- and antidepressant-sensitive 5-HT transporters in the placenta has important implications for the possible effects of these compounds on pregnancy and fetal development.