title: Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease.
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.
authors.affiliation: 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.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: German
authors.affiliation: 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.
authors.forename: Michelle G
authors.initials: MG
authors.lastname: Baladi
authors.affiliation: 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.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: McFadden
authors.affiliation: 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.
authors.forename: Glen R
authors.initials: GR
authors.lastname: Hanson
authors.affiliation: 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 fleckenstein@hsc.utah.edu.
authors.forename: Annette E
authors.initials: AE
authors.lastname: Fleckenstein
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D002493:Central Nervous System Diseases / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000494:pharmacology* / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D015398:Signal Transduction; D009435:Synaptic Transmission; D050493:Vesicular Monoamine Transport Proteins / Q000145:classification / Q000494:pharmacology* / Q000502:physiology*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D004298:Dopamine