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Gβγ protein activation promotes dopamine efflux trough the Dopamine Transporter

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • J Garcia-Olivares
  • GE Torres
  • SG Amara


Proper function of reward circuitries in the brain requires that the presynaptic dopamine transporter (DAT) efficiently recaptures dopamine (DA). DAT function can be regulated by many intracellular mechanisms including phosphorylation, ubiquitination, and protein-protein interactions. Recently, our laboratory reported a novel mechanism describing the regulation of DAT by G-proteins. Gβγ subunits bind DAT, and upon activation decrease DA uptake. We are now exploring whether activation of Gβγ subunits also affect DA efflux in an amphetamine-dependent or –independent manner. Using a radiolabeled efflux assay, we measured DA efflux in HEK-293 cells stably expressing DAT that were preloaded with [H3]-DA. Activation of Gβγ with the cell permeant peptide mSIRK resulted in a dose-dependent release of DA. This effect was blocked by cocaine and GBR12935 demonstrating that Gβγ activation promotes DA efflux through DAT. Similarly, amperometric recordings demonstrated that mSIRK activation of Gβγ also induced DA release in HEK-293-DAT cells. Taken together, our results suggest that DA efflux through DAT occurs by a G protein-dependent process and this novel mechanism might have important implications in the actions of amphetamine.

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