Multiple drug transporters mediate the placental transport of sulpiride
Multiple drug transporters mediate the placental transport of sulpiride
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多种药物转运蛋白介导舒必利的胎盘转运
DOI：
10.1007/s00204-017-2008-8
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发表时间：
2017-06
影响因子：
6.1
通讯作者：
Huidi Jiang
中科院分区：
文献类型：
--
作者：
Mengru Ba;Zhiyuan Ma;Dongli Sun;Caihong Zheng;Yayun Weng;Xi Yang;Ting Jiang;Huidi Jiang
舒必利是一种典型的抗精神病药物，用于治疗精神分裂症、抑郁症和其他心理障碍。使用体外胎盘灌流模型已经证明，少量舒必利可以通过人体胎盘。然而，胎盘转移的机制尚未阐明。考虑到舒必利的结构，我们推测，在胎盘中表达的转运蛋白可能参与了舒必利跨血-胎盘屏障的摄取。我们研究的目的是确定哪些转运体参与了舒必利的胎盘转运。我们的结果表明，舒必利是人有机阳离子转运蛋白(HOCT)3、人多药耐药蛋白(HMDR)1和人乳腺癌耐药蛋白(HBCRP)的底物。此外，肉碱/有机阳离子转运蛋白(OCTN)2、MDR1和BCRP的抑制剂明显影响舒必利在BeWo细胞(人绒毛膜癌细胞系)中的蓄积。舒必利在原代培养的人滋养层细胞中的蓄积明显受Oct3、OCTN1和OCTN2抑制剂的影响。上述结果表明，hOCTN1和hOCTN2可能参与了舒必利从母体循环到滋养层细胞的摄取，hMDR1和hBCRP介导了从滋养层细胞到母体循环的外流，hOCT3可能参与了舒必利在胎盘和胎儿血液之间的双向转运。
Sulpiride is a typical antipsychotic drug for the treatment of schizophrenia, depression and other psychological disorders. It has been proven that a small amount of sulpiride could cross the human placenta using an ex vivo placental perfusion model. However, the placental transfer mechanism has not been elucidated. Considering the structure of sulpiride, we speculated that the transporters expressed in placenta might be involved in sulpiride uptake across the blood–placenta barrier. The aim of our study was to determine which transporters contributed to the placental transfer of sulpiride. Our results revealed that sulpiride was a substrate of human organic cation transporter (hOCT) 3, human multidrug resistance protein (hMDR) 1 and human breast cancer resistance protein (hBCRP) using transfected cells expressing respective transporters. In addition, the accumulation of sulpiride in BeWo cells (a human choriocarcinoma cell line) was obviously affected by inhibitors of carnitine/organic cation transporter (OCTN) 2, MDR1 and BCRP. The accumulation of sulpiride in primary human trophoblast cells was obviously affected by inhibitors of OCT3, OCTN1 and OCTN2. The above results indicate that hOCTN1 and hOCTN2 likely contribute to the sulpiride uptake from maternal circulation to trophoblast cells, while hMDR1 and hBCRP mediate the efflux from trophoblast cells to maternal circulation, and hOCT3 probably is involved in the bidirectional transport of sulpiride between the placenta and fetal blood.
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影响因子：
4.5
作者：
Mei-juan Tu;Siyuan Sun;Kai Wang;Xue-feng Peng;Ruihan Wang;Li-ping Li-Li-ping-Li-1651122038;S. Zeng;Hui Zhou;
通讯作者：
Mei-juan Tu;Siyuan Sun;Kai Wang;Xue-feng Peng;Ruihan Wang;Li-ping Li-Li-ping-Li-1651122038;S. Zeng;Hui Zhou;
DOI：
10.1620/tjem.141.323
发表时间：
1983-11
期刊：
The Tohoku journal of experimental medicine
影响因子：
--
作者：
T. Fukaya;N. Furuhashi;H. Kono;O. Shinkawa;T. Takahashi;M. Suzuki
通讯作者：
T. Fukaya;N. Furuhashi;H. Kono;O. Shinkawa;T. Takahashi;M. Suzuki
DOI：
10.1152/ajpregu.1993.265.4.r756
发表时间：
1993-10
期刊：
The American journal of physiology
影响因子：
--
作者：
H. Stein;K. Oyama;A. Martinez;B. Chappell;J. Padbury
通讯作者：
H. Stein;K. Oyama;A. Martinez;B. Chappell;J. Padbury
影响因子：
5.5
作者：
Lahjouji, K;Elimrani, I;Mitchell, GA
通讯作者：
Mitchell, GA
影响因子：
5.4
作者：
Liping Ma;Yahong Qin;Zhuowei Shen;H. Bi;Haiyong Hu;Min Huang;Hui Zhou;Lushan Yu;Huidi Jiang;S. Zeng
通讯作者：
Liping Ma;Yahong Qin;Zhuowei Shen;H. Bi;Haiyong Hu;Min Huang;Hui Zhou;Lushan Yu;Huidi Jiang;S. Zeng