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Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G Protein, Gαs.

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Title: Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G Protein, Gαs.
Author(s): Erb SJ; Schappi JM; Rasenick MM
Subject(s): G protein G protein-coupled receptor (GPCR) cyclic AMP (cAMP) depression drug action gas chromatography-mass spectrometry (GC-MS) glia glial cell lipid lipid raft mass spectrometry (MS) membrane trafficking monoamine transporter plasma membrane protein translocation protein-drug interaction protein-lipid interaction selective serotonin reuptake inhibitor (SSRI) serotonin serotonin transporter
Abstract: Depression is a significant public health problem for which currently available medications, if effective, require weeks to months of treatment before patients respond. Previous studies have shown that the G protein responsible for increasing cAMP (Gαs) is increasingly localized to lipid rafts in depressed subjects and that chronic antidepressant treatment translocates Gαs from lipid rafts. Translocation of Gαs, which shows delayed onset after chronic antidepressant treatment of rats or of C6 glioma cells, tracks with the delayed onset of therapeutic action of antidepressants. Because antidepressants appear to specifically modify Gαs localized to lipid rafts, we sought to determine whether structurally diverse antidepressants accumulate in lipid rafts. Sustained treatment of C6 glioma cells, which lack 5-hydroxytryptamine transporters, showed marked concentration of several antidepressants in raft fractions, as revealed by increased absorbance and by mass fingerprint. Closely related molecules without antidepressant activity did not concentrate in raft fractions. Thus, at least two classes of antidepressants accumulate in lipid rafts and effect translocation of Gαs to the non-raft membrane fraction, where it activates the cAMP-signaling cascade. Analysis of the structural determinants of raft localization may both help to explain the hysteresis of antidepressant action and lead to design and development of novel substrates for depression therapeutics.
Issue Date: 2016-09-16
Publisher: American Society for Biochemistry and Molecular Biology
Citation Info: Erb, S. J., Schappi, J. M. and Rasenick, M. M. Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G Protein, Gαs. Journal of Biological Chemistry. 2016. 291(38): 19725-19733. doi: 10.1074/jbc.M116.727263.
Type: Article
Description: This is a copy of an article published in the Journal of Biological Chemistry. © 2016 American Society for Biochemistry and Molecular Biology Publications. DOI:10.1074/jbc.M116.727263
URI: http://hdl.handle.net/10027/21401
ISSN: 0021-9258
Date Available in INDIGO: 2017-11-16
 

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