Document Detail


Treatment of C6 glioma cells and rats with antidepressant drugs increases the detergent extraction of G(s alpha) from plasma membrane.
MedLine Citation:
PMID:  10461902     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Results from previous studies suggested that chronic treatment of rats or C6 glioma cells with antidepressants augments the coupling between Gs and adenylyl cyclase. As these effects on C6 glioma cells are seen in the absence of presynaptic input, several antidepressant drugs may have a direct "postsynaptic" effect on their target cells. It was hypothesized that the target of antidepressant action was some membrane protein that may regulate coupling between G proteins and adenylyl cyclase. To test this, C6 glioma cells were treated with amitriptyline, desipramine, iprindole, or fluoxetine for 3 days. Chlorpromazine served as a control for these treatments. Membrane proteins were extracted sequentially with Triton X-100 and Triton X-114 from C6 glioma cells. Triton X-100 extracted more G(s alpha) in membranes prepared from antidepressant-treated C6 glioma cells than from control groups. In addition, cell fractionation studies revealed that the amount of G(s alpha) in caveolin-enriched domains was reduced after antidepressant treatment and that adenylyl cyclase comigrated with G(s alpha) in the gradients. These data suggest that some postsynaptic component that increases availability of Gs to activate effector molecules, such as adenylyl cyclase, might be a target of antidepressant treatment.
Authors:
S Toki; R J Donati; M M Rasenick
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  73     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-09-14     Completed Date:  1999-09-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1114-20     Citation Subset:  IM    
Affiliation:
Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago 60612-7342, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / metabolism
Animals
Antidepressive Agents / pharmacology*
Antidepressive Agents, Tricyclic / pharmacology
Cell Membrane / chemistry,  drug effects,  metabolism
Centrifugation, Density Gradient
Desipramine / pharmacology
Detergents
GTP-Binding Protein alpha Subunits, Gs / biosynthesis*,  chemistry,  isolation & purification
Glioma
Humans
Male
Octoxynol
Polyethylene Glycols
Rats
Rats, Sprague-Dawley
Solubility
Sucrose
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
HL 07692-09/HL/NHLBI NIH HHS; MH39595/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Antidepressive Agents; 0/Antidepressive Agents, Tricyclic; 0/Detergents; 0/Polyethylene Glycols; 50-47-5/Desipramine; 57-50-1/Sucrose; 9002-93-1/Octoxynol; 9036-19-5/Nonidet P-40; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gs; EC 4.6.1.1/Adenylate Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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