Alpha-2 and Beta-2 Adrenoreceptor Coupling To Adenylate Cyclase in Panic Disorder: Effect of Imipramine Treatment

Abstract

Adrenergic receptor (AR) coupling to adenylate cyclase (AC) and the effect of imipramine on AR coupling have not been examined in panic disorder (PD). Platelets alpha-2 AR were measured (Garcia-Sevilla et al., 1981), in 21 normal controls (NC) and 20 PD patients. Neutrophils beta-2 AR were measured (Davis & Leftowitz, 1980), in 34 NC and 27 PD patients. Assays were repeated in 10 patients on imipramine. Saturation and agonist-displacement experiments were conducted and receptor density in the high- and low-conformational states, (RH & RL) and agonist affinity (KH & KL) were measured. The %RH and the KL/KH ratio were used as indices of AR coupling to AC. PD patient had higher alpha-2 RH (NC: 188.1 ± 73.2 vs PD 349.9 ± 176.6 fmol/mg protein, p<.0004) and RL (NC 121.0 ± 47.4 vs PD 180.7 ± 85.3 fmol/mg protein, p<.008). Beta-2 RH (NC: 29.8 ± 34.6 vs PD: 54.9 ± 28.3 fmol/mg protein, p<.003) and RL (NC: 11.3 ± 9.11 vs PD 30.1 ± 36.1 fmol/mg protein, p<.005) were higher in PD. No differences were observed in KH or KL for either alpha-2 or beta-2 AR. Alpha-2 %RH (NC: 60.3 ± 9.5 vs PD 65.7 ± 5.9, p<.03) and beta-2 KL/KH ratio (NC 187.2 ± 256.1 vs 688.5 ± 838.6, p<.001) were higher in PD. Imipramine normalized a pretreatment trend for lower alpha-2 KL/KH ratio (Pre: 74.8 ± 17.6 vs Post: 117.9 ± 83.6, p<.03), lowered beta-2 RH (Pre: 55.28 ± 28.3 vs Post: 29.0 ± 13.0 fmol/mg protein, p<.009) and decreased its KL/KH ratio by 50%. These results show that imipramine enhances alpha-2 coupling to AC and uncouples beta-2 AR with a net effect of decreasing noradrenergic function.