Beta-adrenoreceptor coupling to GS protein in alcohol dependence, panic disorder, and patients with both conditions.
Ethanol may downregulate G-protein-coupled beta-adrenoreceptors (beta AR). beta AR may also be dysregulated in panic disorder (PD). In clinical samples, many patients have comorbid alcohol dependence (AD) and PD. Therefore, we investigated beta AR coupling in patients with these disorders. We harvested polymorphonuclear leukocytes from 24 healthy volunteers (Vs), and from 22 abstinent AD patients, 7 PD patients, and 9 patients with comorbid AD/PD. beta AR were assayed using saturation and agonist-displacement experiments. Group differences were tested using one-way analysis of variance (ANOVA). All beta AR binding parameters were similar in AD patients and Vs. The ratio of the agonists' dissociation constant from the receptor in the low affinity state (KL) to that in the high affinity state (KH) was significantly higher in PD patients than in AD patients and Vs (930.97 +/- 440.80 vs. 226.2 +/- 94.47 vs. 197.05 +/- 61.03, respectively, p < .01). This finding suggests that beta AR are supercoupled to GS in patients with PD. There was a trend for higher total receptor density (RT) in AD/PD and PD patients (Vs = 39.06 +/- 42.57 vs. AD = 27.93 +/- 23.07 vs. AD/PD = 66.85 +/- 79.02 vs. PD = 68.36 +/- 49.20, p < .08). There were no differences between AD/PD and PD patients, who combined had a significantly higher RT than Vs and AD patients (Vs = 38.95 +/- 8.81 vs. AD = 29.63 +/- 5.07 vs. AD/PD = 67.51 +/- 17.00, fmol/mg protein, p < .04). Finally, AD/PD patients had a significantly higher receptor density in the low-affinity conformational state than Vs and AD patients, but not PD patients (25.96 +/- 11.59 vs. 10.69 +/- 1.53 vs. 7.62 +/- 1.08 vs. 17.07 +/- 5.26 fmol/mg protein, respectively, p < .005). beta AR function in polymorphonuclear leukocytes is normal in abstinent alcoholics. The previously reported abnormal beta AR regulation in alcoholism may be state dependent. The higher RT and KL/KH ratio in AD/PD and PD, but not in AD patients, suggest that increased beta AR function may be important in the pathophysiology of PD.
Gurguis
G N
GN
Psychiatry Service, Department of Veterans, Affairs Medical Center, Dallas, TX, USA.
Turkka
J
J
George
D T
DT
Linnoila
M
M
D000318:Adrenergic beta-Agonists / Q000378:metabolism; D000328:Adult; D000437:Alcoholism / Q000150:complications / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D016584:Panic Disorder / Q000150:complications / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D019205:GTP-Binding Protein alpha Subunits, Gs