Adrenergic receptor function in panic disorder. I. Platelet α2 receptors G(i) protein coupling, Effects of imipramine, and relationship to treatment outcome

George N M Gurguis, Debra Antai-Otong, Stephanie P. Vo, Jaishri E. Blakeley, Paul J. Orsulak, Frederick Petty, A. J. Rush

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Various studies suggest α2-adrenergic receptor (α2AR) dysregulation in panic disorder (PD). Platelet α2-AR exist in high- and low-conformational states as a function of their coupling to G(i) protein. α2AR coupling is important in signal transduction and is modulated by antidepressants. α2AR density in the high- and low-conformational states, agonist affinity, and coupling efficiency were investigated in 21 healthy controls, 21 drug-free PD patients, and eight imipramine-treated patients using norepinephrine displacement of 3H-yohimbine binding. Percentage of receptors in the high-conformational state (%R(H)) and the ratio of the agonist dissociation constant to the receptor in the low-/high-conformational state (K(L)/K(H)), calculated from displacement experiments, were used as coupling indices. Patients had high α2AR density in both conformational states. %R(H) and K(L)/K(H) ratio were significantly different, particularly in patients with Hamilton scale for depression (HAMD) scores ≥15. Imipramine treatment (29 weeks) had no effect on α2AR density or coupling, despite improvement in anxiety ratings. High pretreatment α2AR density and coupling predicted low severity of anxiety after treatment. Increased α2AR density and abnormal coupling may represent an adaptive mechanism or trait marker in PD. Copyright (C) 1999 American College of Neuropsychopharmacology.

Original languageEnglish (US)
Pages (from-to)162-176
Number of pages15
JournalNeuropsychopharmacology
Volume20
Issue number2
DOIs
StatePublished - Feb 1 1999

Keywords

  • Alpha-adrenergic receptors
  • Anxiety
  • Coupling
  • Depression
  • G Protein
  • Panic disorder

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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