Publication Date:
1999-07-31
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ramamoorthy, S -- Blakely, R D -- DA07390/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 1999 Jul 30;285(5428):763-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Center for Molecular Neuroscience, School of Medicine, Vanderbilt University, Nashville, TN 37232-6420, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10427004" target="_blank"〉PubMed〈/a〉
Keywords:
Antidepressive Agents/metabolism/pharmacology
;
Biogenic Monoamines/metabolism/pharmacology
;
Biotinylation
;
Carrier Proteins/antagonists & inhibitors/*metabolism
;
Cell Line
;
Central Nervous System Agents/metabolism/*pharmacology
;
Cocaine/metabolism/pharmacology
;
Dextroamphetamine/metabolism/pharmacology
;
Enzyme Activation
;
Humans
;
Ligands
;
Membrane Glycoproteins/antagonists & inhibitors/*metabolism
;
*Membrane Transport Proteins
;
Models, Biological
;
*Nerve Tissue Proteins
;
Neurotransmitter Agents/metabolism/*pharmacology
;
Phosphorylation
;
Protein Kinase C/metabolism
;
Protein Kinases/metabolism
;
Serotonin/*metabolism/pharmacology
;
Serotonin Antagonists/pharmacology
;
Serotonin Plasma Membrane Transport Proteins
;
Serotonin Uptake Inhibitors/metabolism/pharmacology
;
Tetradecanoylphorbol Acetate/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
