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Review ArticleReview Article

Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease

Christopher L. German, Michelle G. Baladi, Lisa M. McFadden, Glen R. Hanson and Annette E. Fleckenstein
Lynette C. Daws, ASSOCIATE EDITOR
Pharmacological Reviews October 2015, 67 (4) 1005-1024; DOI: https://doi.org/10.1124/pr.114.010397
Christopher L. German
School of Dentistry (C.L.G., M.G.B., G.R.H., A.E.F.) and Department of Pharmacology and Toxicology (L.M.M., G.R.H.), University of Utah, Salt Lake City, Utah
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Michelle G. Baladi
School of Dentistry (C.L.G., M.G.B., G.R.H., A.E.F.) and Department of Pharmacology and Toxicology (L.M.M., G.R.H.), University of Utah, Salt Lake City, Utah
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Lisa M. McFadden
School of Dentistry (C.L.G., M.G.B., G.R.H., A.E.F.) and Department of Pharmacology and Toxicology (L.M.M., G.R.H.), University of Utah, Salt Lake City, Utah
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Glen R. Hanson
School of Dentistry (C.L.G., M.G.B., G.R.H., A.E.F.) and Department of Pharmacology and Toxicology (L.M.M., G.R.H.), University of Utah, Salt Lake City, Utah
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Annette E. Fleckenstein
School of Dentistry (C.L.G., M.G.B., G.R.H., A.E.F.) and Department of Pharmacology and Toxicology (L.M.M., G.R.H.), University of Utah, Salt Lake City, Utah
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Lynette C. Daws
School of Dentistry (C.L.G., M.G.B., G.R.H., A.E.F.) and Department of Pharmacology and Toxicology (L.M.M., G.R.H.), University of Utah, Salt Lake City, Utah
Roles: ASSOCIATE EDITOR
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Abstract

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.

Footnotes

  • ↵1 C.L.G. and M.G.B. contributed equally as first authors.

  • This research was supported by the National Institutes of Health National Institute on Drug Abuse [Grants R01-DA11389, P01-DA13367, K02-DA019447, K99-DA036012, and R01-DA031883].

  • dx.doi.org/10.1124/pr.114.010397.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 67 (4)
Pharmacological Reviews
Vol. 67, Issue 4
1 Oct 2015
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Review ArticleReview Article

DAT, VMAT2, Neurotoxicity, and Neuroprotection

Christopher L. German, Michelle G. Baladi, Lisa M. McFadden, Glen R. Hanson and Annette E. Fleckenstein
Pharmacological Reviews October 1, 2015, 67 (4) 1005-1024; DOI: https://doi.org/10.1124/pr.114.010397

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Review ArticleReview Article

DAT, VMAT2, Neurotoxicity, and Neuroprotection

Christopher L. German, Michelle G. Baladi, Lisa M. McFadden, Glen R. Hanson and Annette E. Fleckenstein
Pharmacological Reviews October 1, 2015, 67 (4) 1005-1024; DOI: https://doi.org/10.1124/pr.114.010397
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  • Article
    • Abstract
    • I. Overview
    • II. Dopamine and Dopaminergic Terminals: A Brief Introduction
    • III. Dopamine Transporter: Structure and Regulation
    • IV. Vesicular Monoamine Transporter-2: Structure and Regulation
    • V. Dopamine Transporter, Vesicular Monoamine Transporter-2, and Disorders of the Central Nervous System
    • VI. Pharmacological Manipulation of the Dopamine Transporter and Vesicular Monoamine Transporter-2
    • VII. Summary
    • Authorship Contributions
    • Footnotes
    • Abbreviations
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