Phosphorylation and sequestration of serotonin transporters differentially modulated by psychostimulants.

Ramamoorthy S, Blakely RD
Science. 1999 285 (5428): 763-6

PMID: 10427004 · DOI:10.1126/science.285.5428.763

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.

MeSH Terms (24)

Antidepressive Agents Biogenic Monoamines Biotinylation Carrier Proteins Cell Line Central Nervous System Agents Cocaine Dextroamphetamine Enzyme Activation Humans Ligands Membrane Glycoproteins Membrane Transport Proteins Models, Biological Nerve Tissue Proteins Neurotransmitter Agents Phosphorylation Protein Kinase C Protein Kinases Serotonin Serotonin Antagonists Serotonin Plasma Membrane Transport Proteins Serotonin Uptake Inhibitors Tetradecanoylphorbol Acetate

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