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Titolo:
Phosphorylation and sequestration of serotonin transporters differentiallymodulated by psychostimulants
Autore:
Ramamoorthy, S; Blakely, RD;
Indirizzi:
Vanderbilt Univ, Dept Pharmacol, Sch Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 , Sch Med, Nashville, TN 37232 USA Vanderbilt Univ, Ctr Mol Neurosci, Sch Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 , Sch Med, Nashville, TN 37232 USA
Titolo Testata:
SCIENCE
fascicolo: 5428, volume: 285, anno: 1999,
pagine: 763 - 766
SICI:
0036-8075(19990730)285:5428<763:PASOST>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; HUMAN DOPAMINE TRANSPORTER; IMIPRAMINE BINDING-SITES; TRITIATED IMIPRAMINE; NEUROTRANSMITTER TRANSPORTERS; NOREPINEPHRINE TRANSPORTER; STRIATAL SYNAPTOSOMES; FUNCTIONAL REGULATION; SURFACE EXPRESSION; XENOPUS-OOCYTES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
79
Recensione:
Indirizzi per estratti:
Indirizzo: Blakely, RD Vanderbilt Univ, Dept Pharmacol, Sch Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 ashville, TN 37232 USA
Citazione:
S. Ramamoorthy e R.D. Blakely, "Phosphorylation and sequestration of serotonin transporters differentiallymodulated by psychostimulants", SCIENCE, 285(5428), 1999, pp. 763-766

Abstract

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 SEPT 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.

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Documento generato il 20/01/20 alle ore 21:58:15