Neutrophil β2-adrenergic receptor coupling efficiency to Gs protein in subjects with post-traumatic stress disorder and normal controls

George N M Gurguis, Reagan Andrews, Deborah Antai-Otong, Stephanie P. Vo, Jaishri E. Blakeley, Paul J. Orsulak, A. John Rush

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The symptomatology of post-traumatic stress disorder (PTSD) involves sympathetic hyperarousal. Several of these sympathetic symptoms are mediated through end-organ beta2-adrenergic receptors (β2AR). Increased sympathetic activity in PTSD could therefore be due to increased βAR function. This study investigated βAR function in 30 healthy controls and 20 drug-free PTSD patients, βAR binding studies were conducted using antagonist-saturation and agonist-displacement experiments. Measures of β2AR coupling to G(s) protein were derived from agonist-displacement experiments. PTSD patients had significantly higher β2AR density - particularly in the high-conformational state - and higher β2AR coupling than controls, as reflected in a higher percentage of receptors in the high conformational state and a higher ratio of the agonist dissociation constant from the receptor in the low/high- conformational state. Increased βAR function in PTSD is consistent with the symptomatology of this disorder. Increased βAR density and coupling may be consistent with downregulation of βAR density and uncoupling by antidepressants and may underlie their partial efficacy in PTSD. Dysregulation in G(s) protein function is postulated and, agonist-mediated regulation of βAR expression and/or βAR kinase activity in PTSD should be investigated in future studies.

Original languageEnglish (US)
Pages (from-to)131-140
Number of pages10
JournalPsychopharmacology
Volume143
Issue number2
DOIs
StatePublished - 1999

Keywords

  • Anxiety
  • Beta-adrenergic receptor
  • Coupling
  • Depression
  • G protein
  • Post-traumatic stress disorder

ASJC Scopus subject areas

  • Pharmacology

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