Adrenergic receptor function in panic disorder - I. Platelet alpha(2) receptors: G(i) protein coupling, effects of imipramine, and relationship to treatment outcome

Various studies suggest alpha(2)-adrenergic receptor (alpha(2)AR) dysregula tion in panic disorder (PD). Platelet alpha(2)-AR exist in high- and low-co nformational states as a function of their coupling to G(i) protein, alpha( 2)-AR coupling is important in signal transduction and is modulated by anti depressants. alpha(2)AR 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 imipiramine-treated patients using norepinephrine displacement of H-3-yohimbine binding. Percentage of r eceptors in the high-conformational state (%R-H) and the ratio of the agoni st dissociation constant to the receptor in the low-/high-conformational st ate (K-L/K-H), calculated from displacement experiments, were used as coupl ing indices. Patients had high alpha(2)AR density in both conformational st ates. %R-H and K-L/K-H ratio were significantly different, particularly in patients with Hamilton scale for depression (HAMD) scores greater than or e qual to 15, Imipramine treatment (29 weeks) had no effect on alpha(2)AR den sity or coupling, despite improvement in anxiety ratings. High pretreatment alpha(2)AR density and coupling predicted low severity of anxiety after tr eatment. Increased alpha(2)AR density and abnormal coupling may represent a n adaptive mechanism or trait marker in PD. [Neuropsychopharmacology 20:162 -276, 1999] (C) 1998 American College of Neuropsychopharmacology.