Phosphorylation and sequestration of serotonin transporters differentially modulated by psychostimulants
Phosphorylation and sequestration of serotonin transporters differentially modulated by psychostimulants
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DOI：
10.1126/science.285.5428.763
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发表时间：
1999-07-30
期刊：
影响因子：
56.9
通讯作者：
Blakely, RD
中科院分区：
文献类型：
--
作者：
Ramamoorthy, S;Blakely, RD
许多精神药物会干扰多巴胺、去甲肾上腺素和5-羟色胺的再吸收。转运能力由与蛋白激酶C(PKC)相关的通路调节，导致转运体的磷酸化和封存。5-羟色胺转运体(SERT)的磷酸化和隔离受到配体占有率的很大影响。可以渗透转运蛋白的配体，如5-羟色胺或苯丙胺，可以阻止PKC依赖的SERT磷酸化。非转运的SERT拮抗剂，如可卡因和抗抑郁药，允许SERT磷酸化，但阻断了5-羟色胺的作用。依赖PKC的SEPT封存也被5-羟色胺阻断。这些发现揭示了神经递质再摄取的活动依赖性调节，并确定了安非他明、可卡因和抗抑郁作用以前未知的后果。
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.