REDUCED BETA-ADRENERGIC RECEPTOR-COUPLED GS PROTEIN FUNCTION AND GS-ALPHA IMMUNOREACTIVITY IN MONONUCLEAR LEUKOCYTES OF PATIENTS WITH DEPRESSION

beta-Adrenergic receptor-coupled Gs protein function was measured in 2 6 depressed patients through cholera toxin-sensitive, isoproterenol-in duced increases in H-3-Gpp(NH)p binding capacity to mononuclear leukoc ytes (MNL), Highly significant reductions in receptor-coupled Gs prote in function were observed in the depressed patients: 2.0 +/- 1.3% incr eases in guanine nucleotide-binding capacity, in comparison with the c ontrol group values of 28.3 +/- 6.9%, Similar reductions in Gs protein function were detected in both uni- and bipolar depressed patients. A significant negative correlation was found between receptor-coupled G s protein measures and the severity of depression, Adding semiquantita tive measures of MNL Gs alpha through immunoblot analysis by use of po lyclonal antibodies against Gs alpha subunit, it was found that Gs alp ha relative immunoreactivity was reduced from 100 +/- 2.0% in the cont rol group of subjects to 75.9 +/- 2.3% in the depressed patients. We h ave previously described hyperfunctional Gs proteins in leukocytes of patients with mania. The present findings of reduced function of Gs in depressed patients suggests receptor-coupled Gs protein activity as a biochemical parameter indicatory of the affective state, Reduced rece ptor-coupled Gs protein function may reflect reduced levels of the bet a-adrenergic receptor previously shown in leukocytes of depressed pati ents; however our complementary immunoblot studies suggest a direct, p ostreceptor, quantitative and functional reduction in Gs protein in MN L of depressed patients.