title: Phosducin-like protein levels in leukocytes of patients with major depression and in rat cortex: the effect of chronic treatment with antidepressants.
abstract: The importance of signal transduction processes beyond receptors involving receptor-G protein coupling, in both the pathophysiology and the treatment of mood disorders, is well documented. Thus, regulatory elements of G protein function may play a role in the molecular mechanisms underlying these alterations. Phosducin-like proteins, a family of regulators of G protein function expressed throughout brain and body, modulate G protein function by high affinity sequestration of G protein-betagamma subunits, thus impeding G protein-mediated signal transmission by both Galpha and Gbetagamma subunits. An important consequence of Gbetagamma neutralization is the prevention of G protein-coupled receptor kinase phosphorylation resulting in a temporary protection to agonist-bound receptor desensitization. Phosducin-like protein levels were measured in brain cortices of rats chronically treated with one of five classes of antidepressants: imipramine, venlafaxine, maprotiline, citalopram, and moclobemide. None of the antidepressant treatments had any significant effect on phosducin-like protein levels. Phosducin-like protein levels were evaluated in mononuclear leukocytes from a group of 15 patients diagnosed with major depressive episode, both before the initiation of antidepressant treatment and after 4 weeks of antidepressant medication. No protein changes were found in leukocytes of either untreated patients with major depressive disorder or after 4 weeks of the treatment in comparison with healthy volunteers.
authors.affiliation: Department of Pharmacology, P.O. Box 653, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
authors.forename: Angela
authors.initials: A
authors.lastname: Matuzany-Ruban
authors.forename: Gabriel
authors.initials: G
authors.lastname: Schreiber
authors.forename: Peter
authors.initials: P
authors.lastname: Farkash
authors.forename: Sofia
authors.initials: S
authors.lastname: Avissar
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002352:Carrier Proteins; D002540:Cerebral Cortex / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004334:Drug Administration Schedule; D005136:Eye Proteins / Q000097:blood*; D005260:Female; D020555:GTP-Binding Protein Regulators / Q000097:blood*; D044387:GTP-Binding Protein beta Subunits / Q000097:blood; D044388:GTP-Binding Protein gamma Subunits / Q000097:blood; D019204:GTP-Binding Proteins / Q000097:blood; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D016037:Single-Blind Method
chemical_list: D000928:Antidepressive Agents; D002352:Carrier Proteins; D005136:Eye Proteins; D020555:GTP-Binding Protein Regulators; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D018832:Molecular Chaperones; D008996:Monoamine Oxidase Inhibitors; D009419:Nerve Tissue Proteins; C098789:PDCL protein, human; C498320:Pdcl protein, rat; D010750:Phosphoproteins; C065631:phosducin; D019204:GTP-Binding Proteins