Neutrophil beta2-adrenergic receptor coupling efficiency to Gs protein in subjects with post-traumatic stress disorder and normal controls

• Published in: Psychopharmacology Vol. 143; no. 2; pp. 131 - 140
• Main Authors: Gurguis, G N, Andrews, R, Antai-Otong, D, Vo, S P, Blakeley, J E, Orsulak, P J, Rush, A J
• Format: Journal Article
• Language: English
• Published: Germany 01.04.1999
• Subjects: Adult; Female; GTP-Binding Protein alpha Subunits, Gs - metabolism; Humans; Male; Neutrophils - metabolism; Protein Binding; Protein Conformation; Psychiatric Status Rating Scales; Receptors, Adrenergic, beta-2 - metabolism; Stress Disorders, Post-Traumatic - metabolism; Stress Disorders, Post-Traumatic - psychology
• ISSN: 0033-3158

The symptomatology of post-traumatic stress disorder (PTSD) involves sympathetic hyperarousal. Several of these sympathetic symptoms are mediated through end-organ beta2-adrenergic receptors (beta2AR). Increased sympathetic activity in PTSD could therefore be due to increased betaAR function. This study investigated betaAR function in 30 healthy controls and 20 drug-free PTSD patients. BetaAR binding studies were conducted using antagonist-saturation and agonist-displacement experiments. Measures of beta2AR coupling to Gs protein were derived from agonist-displacement experiments. PTSD patients had significantly higher beta2AR density particularly in the high-conformational state and higher beta2AR coupling than controls, as reflected in a higher percentage of receptors in the high conformational state and a higher ratio of the agonist dissociaton constant from the receptor in the low/high-conformational state. Increased betaAR function in PTSD is consistent with the symptomatology of this disorder. Increased betaAR density and coupling may be consistent with downregulation of betaAR density and uncoupling by antidepressants and may underlie their partial efficacy in PTSD. Dysregulation in Gs protein function is postulated and, agonist-mediated regulation of betaAR expression and/or betaAR kinase activity in PTSD should be investigated in future studies.