CELLULAR TARGETS FOR ABUSABLE DRUGS IN HUMAN PLACENTA

人胎盘中可滥用药物的细胞靶点

• 批准号: 2897993
• 负责人: VADIVEL GANAPATHY
• 金额: $ 26.28万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2897993
• 关键词: amphetamines; brush border membrane; choriocarcinoma; clinical research; cocaine; dopamine; embryo /fetus toxicology; female; human fetus tissue; human subject; laboratory rat; neurotransmitter transport; norepinephrine; nucleotides; placenta; preeclampsia; reproductive system pharmacology; serotonin; serotonin transporter; tissue /cell culture; trophoblast; vesicle /vacuole; women's health

DESCRIPTION: (Applicant's Abstract) Abuse of illicit drugs during pregnancy is currently a serious concern pertaining to women's health because of the deleterious effects these drugs have on the mother and on the fetus. The objective of the current project is to investigate the role of placenta in the pathogenesis of complications arising from abuse of cocaine and amphetamines during pregnancy and to establish that placenta is a direct target for these drugs. Human placenta expresses the serotonin transporter and the norepinephrine transporter, both of which are targets for cocaine and/or amphetamines. These transporters most likely function in the clearance of the vasoactive monoamines serotonin and norepinephrine from the intervillous space. Interference with their functions by cocaine and amphetamines would have had effects on the developing fetus. The current project will investigate the normal function, regulation, and ontogeny of these two transporters in the placenta. Studies will include detailed characterization of the interaction of cocaine and amphetamines with these two transporters. These studies will be done with isolated plasma membrane vesicles from the placenta and also with intact trophoblast cells and choriocarcinoma cells. The placental syncytiotrophoblast is a polarized cell and immunolocalization studies will be performed to determined whether or not the expression of the serotonin and norepinephrine transporters is polarized with regard to the maternal-facing brush border membrane and the fetal-facing basal membrane. Proposed studies will also delineate the differential role of hormones/cytokines in the modulation of these transporters using primary trophoblast cultures and choriocarcinoma cells. These studies will include analysis of hormone/cytokine-induced changes in the transport activity, transporter density and steady state levels of transporter-specific mRNAs. The specific signalling pathways mediating the hormone/cytokine effects will be identified and the involvement of transcriptional and translational processes and posttranslational modifications in the regulation will be delineated. Studies will also test the hypothesis that impaired function of one or both of these transporters is a pathogenic factor in preeclampsia, a condition which clinically resembles in many respects the complications arising from use of cocaine and amphetamines during pregnancy. The ontogenic development of the serotonin and norepinephrine transporters in placenta will be studied using the rat as the experimental model.

描述：（申请人摘要）

项目成果

Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter.

• 发表时间: 1999-09
• 期刊: The Journal of pharmacology and experimental therapeutics
• 作者: Xiang Wu;Wei-qun Huang;P. Prasad;P. Seth;Deva P. Rajan;F. Leibach;Jinwen Chen;S. Conway;V. Ganapathy

Identity of the F52F12.1 gene product in Caenorhabditis elegans as an organic cation transporter.

秀丽隐杆线虫中 F52F12.1 基因产物作为有机阳离子转运蛋白的身份。

• DOI: 10.1016/s0005-2736(99)00020-6
• 发表时间: 1999
• 期刊: Biochimica et biophysica acta
• 作者: Wu,X;Fei,YJ;Huang,W;Chancy,C;Leibach,FH;Ganapathy,V
• 通讯作者: Ganapathy,V

Transport of N-acetylaspartate by the Na(+)-dependent high-affinity dicarboxylate transporter NaDC3 and its relevance to the expression of the transporter in the brain.

Na()依赖性高亲和力二羧酸转运蛋白NaDC3对N-乙酰天冬氨酸的转运及其与大脑中转运蛋白表达的相关性。

• 发表时间: 2000
• 期刊: The Journal of pharmacology and experimental therapeutics.
• 作者: Huang,W;Wang,H;Kekuda,R;Fei,YJ;Friedrich,A;Wang,J;Conway,SJ;Cameron,RS;Leibach,FH;Ganapathy,V
• 通讯作者: Ganapathy,V

Placental transporters relevant to drug distribution across the maternal-fetal interface.

• 发表时间: 2000-08
• 期刊: The Journal of pharmacology and experimental therapeutics
• 作者: V. Ganapathy;P. Prasad;M. E. Ganapathy;F. Leibach

Molecular cloning and functional characterization of a polyspecific organic anion transporter from Caenorhabditis elegans.

秀丽隐杆线虫多特异性有机阴离子转运蛋白的分子克隆和功能表征。

• 发表时间: 1999
• 期刊: The Journal of pharmacology and experimental therapeutics
• 作者: George,RL;Wu,X;Huang,W;Fei,YJ;Leibach,FH;Ganapathy,V
• 通讯作者: Ganapathy,V