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Tricyclic antidepressants, but not the selective serotonin reuptake inhibitor fluoxetine, bind to the S1S2 domain of AMPA receptors
Author(s) -
Gentile Lisa Nancy,
Seguin Sandlin,
Stoll Laura
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a43
Subject(s) - ampa receptor , kainate receptor , chemistry , nbqx , ionotropic effect , silent synapse , pharmacology , glutamate receptor , glutamatergic , neuroscience , metabotropic glutamate receptor 8 , receptor , biology , biochemistry
Recently, the hypothesis that depression is caused solely by a decrease in the synaptic availability of monoaminergic neurotransmitters has been questioned. Based on accumulating data, it seems more plausible that a 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 the NMDA ( N ‐methyl‐D‐aspartate), AMPA (amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid), and kainate receptors. In this talk, data will be presented which shows that five tricyclic antidepressants bind to the S1S2 domain of the GluR2 subunit of the AMPA receptor. A combination of fluorescence quenching, Stern‐Volmer analysis, 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. This data provides further support for a role of the glutamatergic system in antidepressant activity. This work was supported by ACS‐PRF and NSF‐CAREER.