Neutrophil beta(2)-adrenoceptor function in major depression: G(s) coupling, effects of imipramine and relationship to treatment outcome.
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.
Gurguis
G N
GN
The Department of Veterans Affairs Medical Center, Dallas, TX, USA. gurguis.george@dallas.va.gov
Vo
S P
SP
Griffith
J M
JM
Rush
A J
AJ
D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D006801:Humans; D007099:Imipramine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D012044:Regression Analysis; D012720:Severity of Illness Index; D016896:Treatment Outcome
D018759:Adrenergic Uptake Inhibitors; D000929:Antidepressive Agents, Tricyclic; D018343:Receptors, Adrenergic, beta-2; D019205:GTP-Binding Protein alpha Subunits, Gs; D007099:Imipramine