Tricyclic antidepressants, but not the selective serotonin reuptake inhibitor fluoxetine, bind to the S1S2 domain of AMPA receptors
- 作者：Laura Stoll ; S ; lin Seguin ; Lisa Gentile
- 关键词：Tricyclic antidepressants ; Ionotropic glutamate receptors ; AMPA ; Fluoxetine ; S1S2 ; Selective serotonin reuptake inhibitor
- 刊名：Archives of Biochemistry and Biophysics
- 出版年：2007
- 期刊代码：116_00039861
- 类别：ch
- 出版时间：15 February 2007
- 卷：458
- 期：2
- 页码：213-219
- 文件大小：616 K
摘要
The hypothesis that depression is caused solely by a decrease in synaptic availability of monoaminergic neurotransmitters has been questioned over the past two decades. Based on accumulating data, it seems more plausible that cross-talk exists between neurotransmitters in the CNS, including the glutamatergic system. Glutamate, the major fast excitatory neurotransmitter in the CNS, is the natural agonist for the ionotropic glutamate receptors, a family of ligand-gated ion channels including NMDA (N-methyl-d-aspartate), AMPA (amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), and kainate receptors. In this work, we show that five tricyclic antidepressants bind to the S1S2 domain of the GluR2 subunit of the AMPA receptor. A combination of fluorescence quenching, Stern–Volmer analyses, and protease protection assays differentiate the binding of each antidepressant. These analyses provide no evidence for the binding of the selective serotonin reuptake inhibitor, fluoxetine, to this domain. The data presented provides further support for a role of the glutamatergic system in antidepressant activity.