title: Differential effects of antidepressants escitalopram versus lithium on Gs alpha membrane relocalization.
abstract: BACKGROUND
  Plasma membrane localization can play a significant role in the ultimate function of certain proteins. Specific membrane domains like lipid rafts have been shown to be inhibitory domains to a number of signaling proteins, including Gsα, and chronic antidepressant treatment facilitates Gs signaling by removing Gsα form lipid rafts. The intent of this study is to compare the effects of the selective serotnin reuptake inhibitor, escitalopram, with that of the mood stabilizing drug, lithium.
  
  
  RESULTS
  There are a number of mechanisms of action proposed for lithium as a mood stabilizing agent, but the interactions between G proteins (particularly Gs) and mood stabilizing drugs are not well explored. Of particular interest was the possibility that there was some effect of mood stabilizers on the association between Gsα and cholesterol-rich membrane microdomains (lipid rafts), similar to that seen with long-term antidepressant treatment. This was examined by biochemical and imaging (fluorescence recovery after photobleaching: FRAP) approaches. Results indicate that escitalopram was effective at liberating Gsα from lipid rafts while lithium was not.
  
  
  CONCLUSIONS
  There are a number of drug treatments for mood disorders and yet there is no unifying hypothesis for a cellular or molecular basis of action. It is evident that there may in fact not be a single mechanism, but rather a number of different mechanisms that converge at a common point. The results of this study indicate that the mood stabilizing agent, lithium, and the selective serotonin reuptake inhibitor, escitalopram, act on their cellular targets through mutually exclusive pathways. These results also validate the hypothesis that translocation of Gsα from lipid rafts could serve as a biosignature for antidepressant action.
authors.affiliation: Departments of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612-7342, USA. rdonati@ico.edu.|Basic and Health Science Department, Illinois College of Optometry, Chicago, IL, 60616, USA. rdonati@ico.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Donati
authors.affiliation: Departments of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612-7342, USA. jschap3@uic.edu.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schappi
authors.affiliation: Departments of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612-7342, USA. aczysz2@uic.edu.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Czysz
authors.affiliation: Departments of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612-7342, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Jackson
authors.affiliation: Departments of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612-7342, USA. RAZ@uic.edu.|The Psychiatric Institute, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612-7342, USA. RAZ@uic.edu.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Rasenick
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018692:Antimanic Agents / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015283:Citalopram / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D036681:Fluorescence Recovery After Photobleaching; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D018020:Lithium Compounds / Q000494:pharmacology*; D021962:Membrane Microdomains / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D018692:Antimanic Agents; D015283:Citalopram; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D018020:Lithium Compounds; D017367:Selective Serotonin Reuptake Inhibitors; D014635:Valproic Acid