Neutrophil β2-adrenoceptor function in major depression: G(s) coupling, effects of imipramine and relationship to treatment outcome

George N M Gurguis, Stephanie P. Vo, Jay M. Griffith, A. John Rush

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Abnormal β2-adrenoceptor density and β2-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 β2-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 β2-adrenoceptor coupling and density were normal in patients as a whole. Chronic imipramine induced β2-adrenoceptor uncoupling. This effect was observed in treatment responders who had increased β2-adrenoceptor density in the high- conformational state and supercoupling prior to treatment. β2-adrenoceptor density decreased after imipramine treatment. Treatment non-responders had seemingly normal pretreatment β2-adrenoceptor function, which was not changed by imipramine. Differences in β2-adrenoceptor regulation in major depressive disorder may underlie treatment response. The results indirectly implicate abnormal agonist-mediated β2-adrenoceptor gene expression, protein kinase A, and protein kinase C in major depressive disorder.

Original languageEnglish (US)
Pages (from-to)135-144
Number of pages10
JournalEuropean Journal of Pharmacology
Volume386
Issue number2-3
DOIs
StatePublished - Dec 15 1999

Keywords

  • Antidepressant
  • Anxiety
  • Coupling
  • Depression
  • G(s) protein
  • Major
  • Neutrophil
  • Tricyclic
  • β-adrenoceptor

ASJC Scopus subject areas

  • Pharmacology

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