β-Adrenoceptor coupling to G(s) protein in alcohol dependence, panic disorder, and patients with both conditions

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Abstract

Ethanol may down-regulate G-protein-coupled beta-adrenoceptors (βAR). βAR may also be dysregulated in panic disorder (PD). 61 clinical samples, many patients have comorbid alcohol dependence (AD) and PD. Therefore, we investigated βAR 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. βAR were assayed using saturation and agonist-displacement experiments. Group differences were tested using one-way analysis of variance (ANOVA). All βAR binding parameter were similar in AD patients and Vs. The ratio of the agonists' dissociation constant from the receptor in the low affinity state (K(L)) to that in the high affinity state (K(H)) 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 βAR are supercoupled to G(s) in patients with PD. There was a trend for higher total receptor density (R(T)) 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 R(T) than V(s) 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). βAR function in polymorphonuclear leukocytes is normal in abstinent alcoholics. The previously reported abnormal βAR regulation is alcoholism may be state dependent. The higher R(T) and K(L)/K(H) ratio in AD/PD and PD, but not in the AD patients, suggest that increased βAR function may be important in the pathophysiology of PD.

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Gurguis, G. N. M., Turkka, J., George, D. T., & Linnoila, M. (1997). β-Adrenoceptor coupling to G(s) protein in alcohol dependence, panic disorder, and patients with both conditions. Neuropsychopharmacology, 16(1), 69–76. https://doi.org/10.1016/S0893-133X(96)00161-3

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