Eshleman A J, Henningsen R A, Neve K A, Janowsky A
Research Service, Veterans Affairs Medical Center, Portland, Oregon.
Mol Pharmacol. 1994 Feb;45(2):312-6.
A human dopamine transporter cDNA was cloned and transfected into COS-7 cells, a cell line that lacks vesicular storage and release mechanisms. Cells expressing the dopamine transporter acquired the capacity to take up and release dopamine via the transporter. Ionic conditions that stimulate inside-out transport in vivo, such as depolarizing concentrations of K+ or low concentrations of extracellular Na+, were found to stimulate Ca(2+)-independent release of [3H]dopamine from transfected COS-7 cells. Dopamine uptake inhibitors had one of three effects on transporter-mediated efflux. Some drugs, in addition to inhibiting uptake, inhibited spontaneous release of dopamine. Drugs in this class included mazindol, GBR-12935, bupropion, nomifensine, and benztropine. All of the drugs with the potential for abuse by humans either enhanced release (methamphetamine, amphetamine, and ethanol) or had no effect on release (phencyclidine, cocaine, and WIN 35,428). The ability to define classes of uptake blockers based on their effects on human transporter-mediated dopamine efflux may lead to the identification of structural features of the transporter that differentiate abused from nonabused drugs.
人类多巴胺转运体cDNA被克隆并转染到COS - 7细胞中，COS - 7细胞系缺乏囊泡储存和释放机制。表达多巴胺转运体的细胞获得了通过该转运体摄取和释放多巴胺的能力。发现在体内刺激内翻外转运的离子条件，如去极化浓度的K⁺或低浓度的细胞外Na⁺，可刺激转染的COS - 7细胞中[³H]多巴胺的钙非依赖性释放。多巴胺摄取抑制剂对转运体介导的流出有三种作用之一。一些药物除了抑制摄取外，还抑制多巴胺的自发释放。这类药物包括吗茚酮、GBR - 12935、安非他酮、诺米芬辛和苯海索。所有有被人类滥用可能性的药物要么增强释放（甲基苯丙胺、苯丙胺和乙醇），要么对释放没有影响（苯环己哌啶、可卡因和WIN 35,428）。根据摄取阻滞剂对人类转运体介导的多巴胺流出的影响来定义摄取阻滞剂类别，可能会导致识别出区分被滥用药物和未被滥用药物的转运体结构特征。
