PDF(Sci-hub)
Abstract：
Lamotrigine (LTG) is an important antiepileptic drug for the treatment of seizures in pregnant women with epilepsy. However, it is not known if the transport of LTG into placental cells occurs via a carrier-mediated pathway. The aim of this study was to investigate the uptake properties of LTG into placental cell lines (BeWo and JEG-3), and to determine the involvement of organic cation transporters (OCTs, SLC22A1-3) and organic cation/carnitine transporter (OCTNs, SLC22A4-5) in the uptake process. The uptake of LTG at 37 °C was higher than that at 4 °C. OCT1 and OCTNs were detected in both cell lines. The uptake of LTG was not greatly affected by the extracellular pH, Na+-free conditions, or the presence of l-carnitine, suggesting that OCTNs were not involved. Although several potent inhibitors of OCTs (chloroquine, imipramine, quinidine, and verapamil) inhibited LTG uptake, other typical inhibitors had no effect. In addition, siRNA targeted to OCT1 had no significant effect on LTG uptake. The mRNA expression in human term placenta followed the order OCTN2 > OCT3 > OCTN1 > OCT1 ≈ OCT2. These observations suggested that LTG uptake into placental cells was carrier-mediated, but that OCTs and OCTNs were not responsible for the placental transport process.
摘要：
拉莫三嗪（LTG）是一种重要的抗癫痫药物，用于治疗妊娠合并癫痫妇女的癫痫发作。然而,尚不清楚LTG是否通过载体介导的途径转运到胎盘细胞中。这项研究的目的是研究LTG在胎盘细胞系（BeWo和JEG-3）中的摄取特性，并确定有机阳离子转运蛋白(OCTs，SLC22A1-3)和有机阳离子/肉碱转运蛋白(OCTNs，SLC22A4-5）在摄取过程中。在37°C时LTG的摄取高于在4°C时的摄取。在两种细胞系中均检测到OCT1和OCTN。LTG的摄取受细胞外pH的影响不年夜，无Na+条件,或者左旋肉碱的存在，表明OCTN没有参与。尽管几种有效的OCTs抑制剂(氯喹，丙咪嗪,奎尼丁,和维拉帕米）抑制LTG摄取，其他典型的抑制剂没有效果。此外,靶向OCT1的siRNA对LTG摄取没有显著影响。人足月胎盘mRNA表达顺序为OCTN2>OCT3>OCTN1>OCT1≈OCT2。这些观察结果表明，LTG对胎盘细胞的摄取是载体介导的，但是OCTs和OCTN不负责胎盘运输过程。
