Gnm. Gurguis et al., Neutrophil beta(2)-adrenergic receptor coupling efficiency to Gs protein in subjects with post-traumatic stress disorder and normal controls, PSYCHOPHAR, 143(2), 1999, pp. 131-140
The symptomatology of post-traumatic stress disorder (PTSD) involves sympat
hetic hyperarousal. Several of these sympathetic symptoms are mediated thro
ugh end-organ beta(2)-adrenergic receptors (beta(2)AR). Increased sympathet
ic activity in PTSD could therefore be due to increased beta AR function. T
his study investigated beta AR function in 30 healthy controls and 20 drug-
free PTSD patients. beta AR binding studies were conducted using antagonist
-saturation and agonist-displacement experiments. Measures of beta(2)AR cou
pling to G(s) protein were derived from agonist-displacement experiments. P
TSD patients had significantly higher beta(2)AR density - particularly in t
he high-conformational state - and higher beta(2)AR coupling than controls,
as reflected in a higher percentage of receptors in the high conformationa
l state and a higher ratio of the agonist dissociaton constant from the rec
eptor in the low/high-conformational state. Increased beta AR function in P
TSD is consistent with the symptomatology of this disorder. Increased beta
AR density and coupling may be consistent with downregulation of beta AR de
nsity and uncoupling by antidepressants and may underlie their partial effi
cacy in PTSD. Dysregulation in G(s) protein function is postulated and, ago
nist-mediated regulation of beta AR expression and/or beta AR kinase activi
ty in PTSD should be investigated in future studies.