Amphetamine-induced decreases in dopamine transporter surface expression are protein kinase C-independent
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UMass Chan Affiliations
Melikian LabDepartment of Biochemistry and Molecular Pharmacology
Department of Psychiatry
Brudnick Neuropsychiatric Research Institute
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2008-01-01Keywords
Amphetamine; Animals; Dopamine; Dopamine Plasma Membrane Transport Proteins; Dopamine Uptake Inhibitors; Endocytosis; Enzyme Inhibitors; Gene Expression Regulation; Mutagenesis; PC12 Cells; Protein Kinase C; Protein Transport; Rats; Time Factors; TransfectionLife Sciences
Medicine and Health Sciences
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Show full item recordAbstract
Amphetamine (AMPH) is a potent dopamine (DA) transporter (DAT) inhibitor that markedly increases extracellular DA levels. In addition to its actions as a DAT antagonist, acute AMPH exposure induces DAT losses from the plasma membrane, implicating transporter-specific membrane trafficking in amphetamine's actions. Despite reports that AMPH modulates DAT surface expression, the trafficking mechanisms leading to this effect are currently not defined. We recently reported that DAT residues 587-596 play an integral role in constitutive and protein kinase C (PKC)-accelerated DAT internalization. In the current study, we tested whether the structural determinants required for PKC-stimulated DAT internalization are necessary for AMPH-induced DAT sequestration. Acute amphetamine exposure increased DAT endocytic rates, but DAT carboxy terminal residues 587-590, which are required for PKC-stimulated internalization, were not required for AMPH-accelerated DAT endocytosis. AMPH decreased DAT endocytic recycling, but did not modulate transferrin receptor recycling, suggesting that AMPH does not globally diminish endocytic recycling. Finally, treatment with a PKC inhibitor demonstrated that AMPH-induced DAT losses from the plasma membrane were not dependent upon PKC activity. These results suggest that the mechanisms responsible for AMPH-mediated DAT internalization are independent from those governing PKC-sensitive DAT endocytosis.Source
Neuropharmacology. 2008 Mar;54(3):605-12. Epub 2007 Nov 22. Link to article on publisher's siteDOI
10.1016/j.neuropharm.2007.11.007Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33764PubMed ID
18164041Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.neuropharm.2007.11.007