Adrenergic receptor function in panic disorder. II. Neutrophil beta 2 receptors: Gs protein coupling, effects of imipramine treatment and relationship to treatment outcome.
Panic attacks are associated with increased autonomic symptoms, suggesting increased beta 2-adrenergic receptor (beta 2AR) function in PD. Tricyclic antidepressants downregulate beta AR function. Previous studies on beta AR function in PD, however, are inconsistent. We recently found increased beta AR coupling and density in neutrophils of symptomatic drug-free PD patients. This study evaluated beta AR coupling to Gs protein in 28 controls, 25 drug-free PD patients and 8 PD imipramine-treated patients. PD patients had significantly higher coupling and receptor density, particularly in the high-conformational state. Differences were more pronounced in patients with less depressive symptomatology. Treatment with imipramine was associated with decreased beta AR coupling and density in the high-conformational state. Several beta AR binding parameters were related to severity of anxiety symptoms and treatment outcome. Antidepressants downregulate beta AR density and induce uncoupling from Gs protein in PD. Future studies may investigate beta AR coupling in relationship to treatment outcome and the role of beta AR kinase in PD.
Department of Veterans Affairs Medical Center, Laboratory of Clinical Neuroscience, Dallas, TX 75216, USA. gurguis.george@dallas.va.gov
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Gurguis
J E
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Blakeley
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Antai-Otong
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P J
PJ
Orsulak
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Petty
A J
AJ
Rush
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology* / Q000627:therapeutic use*; D001667:Binding, Competitive / Q000187:drug effects*; D002452:Cell Count / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000187:drug effects*; D006801:Humans; D007099:Imipramine / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D016584:Panic Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000378:metabolism; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D000929:Antidepressive Agents, Tricyclic; D018343:Receptors, Adrenergic, beta-2; D019205:GTP-Binding Protein alpha Subunits, Gs; D007099:Imipramine