GSBS Student Publications

Title

Amphetamine-induced decreases in dopamine transporter surface expression are protein kinase C-independent

GSBS Program

Biochemistry & Molecular Pharmacology

Publication Date

2008-01-01

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Psychiatry, Brudnick Neuropsychiatric Research Institute; Department of Biochemistry and Molecular Pharmacology

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

DOI of Published Version

10.1016/j.neuropharm.2007.11.007

Source

Neuropharmacology. 2008 Mar;54(3):605-12. Epub 2007 Nov 22. Link to article on publisher's site

Journal/Book/Conference Title

Neuropharmacology

Related Resources

Link to Article in PubMed

PubMed ID

18164041

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