Platelet alpha(2A)-adrenoceptor function in major depression: G(i) 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

25 Citations (Scopus)

Abstract

Studies suggest α(2A)-adrenoceptors (α(2A)AR) dysregulation in major depressive disorder (MDD). Platelet α(2A)ARs exist in high- and low-conformational states that are regulated by G(i) protein. Although α(2A)AR coupling to G(i) protein plays an important role in signal transduction and is modulated by antidepressants, it has not been previously investigated. α2AR density in the high- and low-conformational states, agonist affinity and coupling efficiency were investigated in 27 healthy control subjects, 23 drug-free MDD patients and 16 patients after imipramine treatment using 3H-yohimbine saturation and norepinephrine displacement of 3H-yohimbine binding experiments. Coupling measures were derived from NE-displacement experiments. Patients had significantly higher α(2A)AR density, particularly in the high-conformational state, than control subjects. Coupling indices were normal in patients. High pre-treatment agonist affinity to the receptor in the high-conformational state and normal coupling predicted positive treatment outcome. Decreased coupling to G(i) predicted a negative treatment outcome. Imipramine induced uncoupling (-11%) and redistribution of receptor density in treatment responders only, but had no effect on α(2A)AR coupling or density in treatment non-responders. Increased α(2A)AR density may represent a trait marker in MDD. The results provide indirect evidence for abnormal protein kinase A (PKA) and protein kinase C (PKC) in MDD which may be pursued in future investigations. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)73-95
Number of pages23
JournalPsychiatry Research
Volume89
Issue number2
DOIs
StatePublished - Dec 20 1999

Fingerprint

Imipramine
Major Depressive Disorder
Adrenergic Receptors
Blood Platelets
Depression
Yohimbine
Therapeutics
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C
Antidepressive Agents
Signal Transduction
Norepinephrine
Healthy Volunteers
Proteins
Pharmaceutical Preparations

Keywords

  • Alpha(2A)-adrenoceptors
  • Anxiety
  • Coupling
  • G(i) protein
  • Major depression
  • Platelets
  • Tricyclic antidepressants

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Psychology(all)

Cite this

Platelet alpha(2A)-adrenoceptor function in major depression : G(i) coupling, effects of imipramine and relationship to treatment outcome. / Gurguis, George N M; Vo, Stephanie P.; Griffith, Jay M.; Rush, A. John.

In: Psychiatry Research, Vol. 89, No. 2, 20.12.1999, p. 73-95.

Research output: Contribution to journalArticle

Gurguis, George N M ; Vo, Stephanie P. ; Griffith, Jay M. ; Rush, A. John. / Platelet alpha(2A)-adrenoceptor function in major depression : G(i) coupling, effects of imipramine and relationship to treatment outcome. In: Psychiatry Research. 1999 ; Vol. 89, No. 2. pp. 73-95.
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