RESUMO
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.
Assuntos
Antidepressivos/administração & dosagem , Córtex Cerebral/metabolismo , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Proteínas do Olho/sangue , Reguladores de Proteínas de Ligação ao GTP/sangue , Leucócitos/metabolismo , Inibidores da Monoaminoxidase/administração & dosagem , Fosfoproteínas/sangue , Adolescente , Adulto , Animais , Antidepressivos/uso terapêutico , Proteínas de Transporte , Transtorno Depressivo Maior/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Esquema de Medicação , Feminino , Subunidades beta da Proteína de Ligação ao GTP/sangue , Subunidades gama da Proteína de Ligação ao GTP/sangue , Proteínas de Ligação ao GTP/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares , Inibidores da Monoaminoxidase/uso terapêutico , Proteínas do Tecido Nervoso , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Método Simples-CegoRESUMO
Alterations of cellular G proteins have been implicated in the pathophysiology of some psychiatric disorders. So far, no study assessed G protein function in anorexia nervosa (AN) and bulimia nervosa (BN). Therefore, we measured immunoreactive levels of G(alpha s), G(alpha i), G(alpha q/11) and G(beta) protein subunits in mononuclear leukocytes of 71 drug-free women, including 25 subjects with AN, 26 individuals with BN and 20 healthy controls. As compared to healthy women, anorexic patients exhibited significantly increased levels of G(alpha i) and G(beta) proteins, while bulimic patients had significantly increased levels of G(alpha s), G(alpha i) and G(beta) proteins. Immunoreactive levels of peripheral G protein subunits were not significantly correlated with demographic or nutritional parameters. These findings, although obtained in peripheral blood cells, may suggest a derangement of G protein-mediated signal transduction in the pathophysiology of eating disorders.