Tricyclic Antidepressants, but Not the Selective Serotonin Reuptake Inhibitor Fluoxetine, Bind to the S1s2 Domain of Ampa Receptors.
From: Department of Chemistry, Western Washington University, Bellingham, WA 98225-9150, USA.
Archives of biochemistry and biophysics
- Publish Date: Feb 2007
- ISSN: 0003-9861
- Volume: 458
- Issue: 2
- Pages: 213-9
- Medium: Print
- Language: English
- Citation (JAMA): Stoll Laura, Seguin Sandlin, Gentile Lisa, et al. Tricyclic Antidepressants, but Not the Selective Serotonin Reuptake Inhibitor Fluoxetine, Bind to the S1s2 Domain of Ampa Receptors.. Arch. Biochem. Biophys. Feb 2007;458:213-9
Abstract
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.
Mesh Headings (Keywords): Antidepressive Agents, Second-Generation, Antidepressive Agents, Tricyclic, Binding Sites, DNA, Complementary, Fluoxetine, Mutation, Peptide Hydrolases, Protein Structure, Tertiary, Receptors, AMPA, Serotonin Uptake Inhibitors
Check for Full Text / PubMed Unique Identifier (PMID): 17214956
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