title: Acute and chronic effects of antidepressants on the G-protein alpha subunit profiles in vitro and in vivo.
abstract: OBJECTIVE
  Neurochemical studies on the etiopathogenesis of depression are also focusing on the transduction system beyond receptors. Trimeric G-proteins play a crucial role in the transmembrane signalling, signal amplification and intracellular processing. Abnormalities of G-protein levels are observed in subjects with depression, G-protein modulation is considered to play a role in the antidepressant mode of action.
  
  
  METHODS
  We studied acute or chronic administration of antidepressants from different pharmacological groups. We used immunochemical estimation (ELISA) of the main types of G-protein alpha subunits from isolated membranes of C6 glioma cells and rat brain tissue.
  
  
  RESULTS
  Significant elevation of G alpha q/11 subunits after chronic administration of sertraline and significant reduction of G alpha s subunit levels following both acute and chronic administrations of sertraline were found. In contrast, no significant effects on G alpha subunit levels following acute desipramine and moclobemide administration were observed in vitro. Chronic moclobemide effect in vivo is causing significant elevation of Galpha s and Galpha i1,2 subunit levels.
  
  
  CONCLUSIONS
  Results show involvement of antidepressant drugs in the C6 glioma signal transduction cascades modulation in dependence on the antidepressant class. Significant influence in the cAMP system modulation is observed after administration both SSRI and MAOA inhibitors. Astrocytoma cells - C6 glioma cells also can offer a model system of the glia where modulation of cell signalization cascades can influence cell functioning and production of neurotrophic factor molecules relevant to the antidepressant treatment and depression etiopathogenesis.
authors.affiliation: 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Pav
authors.forename: Hana
authors.initials: H
authors.lastname: Kovaru
authors.forename: Frantisek
authors.initials: F
authors.lastname: Kovaru
authors.forename: Vera
authors.initials: V
authors.lastname: Lisa
authors.forename: Petra
authors.initials: P
authors.lastname: Ondrackova-Zelnickova
authors.forename: Anna
authors.initials: A
authors.lastname: Fiserova
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism*; D045744:Cell Line, Tumor; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000928:Antidepressive Agents; D044385:GTP-Binding Protein alpha Subunits