Platelet alpha(2)-adrenergic receptor coupling efficiency to G(i) protein in subjects with post-traumatic stress disorder and normal controls

Low platelet membrane alpha(2)-adrenergic receptor (alpha(2)AR) density and low basal and forskolin-stimulated cyclic adenosine monophosphate response s, which have been reported in post-traumatic stress disorder (PTSD), sugge st either abnormal alpha(2)AR coupling to G(i) protein or dysregulation in post-receptor signal transduction mechanisms. alpha(2)AR density in the hig h- and low-conformational states, agonist affinity in both states and coupl ing to G(i) protein were investigated in 23 drug-free combat PTSD patients and 25 normal controls. alpha(2)AR coupling measures were not different bet ween PTSD patients and controls. Total alpha(2)AR density was higher in PTS D patients than controls, due to a higher density of the receptor in the hi gh-conformational state. There were no differences in agonist affinity to t he receptor in either conformational state. Results rule out dysregulation in alpha(2)AR coupling to G(i) protein. Studies of post-receptor signal tra nsduction mechanisms are warranted.