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

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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.

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