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Science 30 July 1999:
Vol. 285. no. 5428, pp. 763 - 766
DOI: 10.1126/science.285.5428.763
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Reports

Phosphorylation and Sequestration of Serotonin Transporters Differentially Modulated by Psychostimulants

Sammanda Ramamoorthy, Randy D. Blakely *

Many psychotropic drugs interfere with the reuptake of dopamine, norepinephrine, and serotonin. Transport capacity is regulated by kinase-linked pathways, particularly those involving protein kinase C (PKC), resulting in transporter phosphorylation and sequestration. Phosphorylation and sequestration of the serotonin transporter (SERT) were substantially impacted by ligand occupancy. Ligands that can permeate the transporter, such as serotonin or the amphetamines, prevented PKC-dependent SERT phosphorylation. Nontransported SERT antagonists such as cocaine and antidepressants were permissive for SERT phosphorylation but blocked serotonin effects. PKC-dependent SERT sequestration was also blocked by serotonin. These findings reveal activity-dependent modulation of neurotransmitter reuptake and identify previously unknown consequences of amphetamine, cocaine, and antidepressant action.

Department of Pharmacology and Center for Molecular Neuroscience, School of Medicine, Vanderbilt University, Nashville, TN 37232-6420, USA.
*   To whom correspondence should be addressed. E-mail: randy.blakely{at}mcmail.vanderbilt.edu

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   Abstract »    Full Text »    PDF »
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