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

Journal Article (Clinical Trial;Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Gurguis, GN; Vo, SP; Griffith, JM; Rush, AJ

Published Date

  • December 15, 1999

Published In

Volume / Issue

  • 386 / 2-3

Start / End Page

  • 135 - 144

PubMed ID

  • 10618463

International Standard Serial Number (ISSN)

  • 0014-2999

Digital Object Identifier (DOI)

  • 10.1016/s0014-2999(99)00749-9


  • eng

Conference Location

  • Netherlands