Neutrophil β 2-adrenoceptor function in major depression: G s coupling, effects of imipramine and relationship to treatment outcome

Abstract

Abnormal β 2-adrenoceptor density and β 2-adrenoceptor-mediated cyclic adenosine monophosphate (cAMP) responses were inconsistently reported in major depressive disorder. Tricyclic antidepressants downregulate β-adrenoceptor density and decrease coupling to G s protein. Abnormal β-adrenoceptor coupling may exist in major depressive disorder and may relate to treatment response. We investigated β 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 β 2-adrenoceptor coupling and density were normal in patients as a whole. Chronic imipramine induced β 2-adrenoceptor uncoupling. This effect was observed in treatment responders who had increased β 2-adrenoceptor density in the high-conformational state and supercoupling prior to treatment. β 2-adrenoceptor density decreased after imipramine treatment. Treatment non-responders had seemingly normal pretreatment β 2-adrenoceptor function, which was not changed by imipramine. Differences in β 2-adrenoceptor regulation in major depressive disorder may underlie treatment response. The results indirectly implicate abnormal agonist-mediated β 2-adrenoceptor gene expression, protein kinase A, and protein kinase C in major depressive disorder.