Neutrophil beta(2)-adrenoceptor function in major depression: G(s) coupling, effects of imipramine and relationship to treatment outcome.
Eur J Pharmacol
; 386(2-3): 135-44, 1999 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-10618463
ABSTRACT
Abnormal beta(2)-adrenoceptor density and beta(2)-adrenoceptor-mediated cyclic adenosine monophosphate (cAMP) responses were inconsistently reported in major depressive disorder. Tricyclic antidepressants downregulate beta-adrenoceptor density and decrease coupling to G(s) protein. Abnormal beta-adrenoceptor coupling may exist in major depressive disorder and may relate to treatment response. We investigated beta(2)-adrenoceptor coupling to G(s) protein in 25 controls, 23 major depressive disorder drug-free patients and 16 major depressive disorder patients after chronic imipramine treatment using agonist displacement experiments. Pretreatment beta(2)-adrenoceptor coupling and density were normal in patients as a whole. Chronic imipramine induced beta(2)-adrenoceptor uncoupling. This effect was observed in treatment responders who had increased beta(2)-adrenoceptor density in the high-conformational state and supercoupling prior to treatment. Beta(2)-adrenoceptor density decreased after imipramine treatment. Treatment non-responders had seemingly normal pretreatment beta(2)-adrenoceptor function, which was not changed by imipramine. Differences in beta(2)-adrenoceptor regulation in major depressive disorder may underlie treatment response. The results indirectly implicate abnormal agonist-mediated beta(2)-adrenoceptor gene expression, protein kinase A, and protein kinase C in major depressive disorder.
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Base de dados:
MEDLINE
Assunto principal:
Receptores Adrenérgicos beta 2
/
Subunidades alfa Gs de Proteínas de Ligação ao GTP
/
Transtorno Depressivo Maior
/
Imipramina
/
Antidepressivos Tricíclicos
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
Limite:
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article