Dopamine (DA) plays a well recognized role in a variety of physiologic functions such as movement, cognition, mood, and reward. Consequently, many human disorders are due, in part, to dysfunctional dopaminergic systems, including Parkinson's disease, attention deficit hyperactivity disorder, and substance abuse. Drugs that modify the DA system are clinically effective in treating symptoms of these diseases or are involved in their manifestation, implicating DA in their etiology. DA signaling and distribution are primarily modulated by the DA transporter (DAT) and by vesicular monoamine transporter (VMAT)-2, which transport DA into presynaptic terminals and synaptic vesicles, respectively. These transporters are regulated by complex processes such as phosphorylation, protein-protein interactions, and changes in intracellular localization. This review provides an overview of 1) the current understanding of DAT and VMAT2 neurobiology, including discussion of studies ranging from those conducted in vitro to those involving human subjects; 2) the role of these transporters in disease and how these transporters are affected by disease; and 3) and how selected drugs alter the function and expression of these transporters. Understanding the regulatory processes and the pathologic consequences of DAT and VMAT2 dysfunction underlies the evolution of therapeutic development for the treatment of DA-related disorders.

中文翻译：

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多巴胺和囊泡单胺转运蛋白的调节：药理学目标和对疾病的影响。

多巴胺（DA）在各种生理功能（例如运动，认知，情绪和奖励）中起着公认的作用。因此，许多人类疾病部分是由于多巴胺能系统功能失调所致，包括帕金森氏病，注意力缺陷多动障碍和药物滥用。修饰DA系统的药物在临床上可有效治疗这些疾病的症状或参与其表现，从而将DA纳入其病因。DA信号传导和分布主要受DA转运蛋白（DAT）和水泡单胺转运蛋白（VMAT）-2的调节，后者分别将DA转运到突触前末端和突触小泡中。这些转运蛋白受诸如磷酸化，蛋白质-蛋白质相互作用和细胞内定位变化等复杂过程的调节。这篇综述提供了以下方面的概述：1）对DAT和VMAT2神经生物学的当前了解，包括对从体外进行的研究到涉及人类受试者的研究的讨论；2）这些转运蛋白在疾病中的作用以及这些转运蛋白如何受疾病影响；和3）以及所选药物如何改变这些转运蛋白的功能和表达。了解DAT和VMAT2功能障碍的调节过程和病理后果，是治疗与DA相关疾病的治疗方法发展的基础。2）这些转运蛋白在疾病中的作用以及这些转运蛋白如何受疾病影响；和3）以及所选药物如何改变这些转运蛋白的功能和表达。了解DAT和VMAT2功能障碍的调节过程和病理后果，是治疗与DA相关疾病的治疗方法发展的基础。2）这些转运蛋白在疾病中的作用以及这些转运蛋白如何受疾病影响；和3）以及所选药物如何改变这些转运蛋白的功能和表达。了解DAT和VMAT2功能障碍的调节过程和病理后果，是治疗与DA相关疾病的治疗方法发展的基础。