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Eur J Pharmacol. 2003 Oct 31;479(1-3):83-91.

The effect of phosphorylation on amphetamine-mediated outward transport.

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  • 1Department of Pharmacology, University of Michigan Medical School, 2220E MSRB III, Ann Arbor, MI 48109-0632, USA.


Amphetamine elicits its locomotor-activating and drug-reinforcing effects by releasing the catecholamines dopamine and norepinephrine into the synapse. Amphetamine is a substrate of the plasmalemmal transporters for both dopamine and norepinephrine. As such, it binds to the transporters in conjunction with Na+ and Cl-, facilitating a conformational change leading the transporter to face inward. The subsequent binding of intracellular catecholamine results in an outward transport and release of the catecholamine into the synapse. Both inward and outward transport through the catecholamine transporters are regulated by protein kinases, particularly protein kinase C, but the effect of the enzyme on the two processes appears to be asymmetric. The purpose of this review is to discuss the evidence showing that protein kinase C activation facilitates outward transport through the catecholamine plasmalemmal transporters which may mediate amphetamine action in intact tissue.

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