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Publication : PI3K signaling supports amphetamine-induced dopamine efflux.

First Author  Lute BJ Year  2008
Journal  Biochem Biophys Res Commun Volume  372
Issue  4 Pages  656-61
PubMed ID  18510945 Mgi Jnum  J:137770
Mgi Id  MGI:3802864 Doi  10.1016/j.bbrc.2008.05.091
Citation  Lute BJ, et al. (2008) PI3K signaling supports amphetamine-induced dopamine efflux. Biochem Biophys Res Commun 372(4):656-61
abstractText  The dopamine (DA) transporter (DAT) is a major molecular target of the psychostimulant amphetamine (AMPH). AMPH, as a result of its ability to reverse DAT-mediated inward transport of DA, induces DA efflux thereby increasing extracellular DA levels. This increase is thought to underlie the behavioral effects of AMPH. We have demonstrated previously that insulin, through phosphatidylinositol 3-kinase (PI3K) signaling, regulates DA clearance by fine-tuning DAT plasma membrane expression. PI3K signaling may represent a novel mechanism for regulating DA efflux evoked by AMPH, since only active DAT at the plasma membrane can efflux DA. Here, we show in both a heterologous expression system and DA neurons that inhibition of PI3K decreases DAT cell surface expression and, as a consequence, AMPH-induced DA efflux.
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