Avissar S, Barki-Harrington L, Nechamkin Y, Roitman G, Schreiber G
Department of Clinical Pharmacology, Faculty for Health Sciences, Ben-Gurion University of the Negev, Israel.
Biol Psychiatry. 1996 May 1;39(9):755-60. doi: 10.1016/0006-3223(95)00248-0.
beta-Adrenergic receptor-coupled Gs protein function was measured in 26 depressed patients through cholera toxin-sensitive, isoproterenol-induced increases in 3H-Gpp(NH)p binding capacity to mononuclear leukocytes (MNL). Highly significant reductions in receptor-coupled Gs protein function were observed in the depressed patients: 2.0 +/- 1.3% increases in guanine nucleotide-binding capacity, in comparison with the control 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 Gs protein measures and the severity of depression. Adding semiquantitative measures of MNL Gs alpha through immunoblot analysis by use of polyclonal antibodies against Gs alpha subunit, it was found that Gs alpha relative immunoreactivity was reduced from 100 +/- 2.0% in the control group of subjects to 75.9 +/- 2.3% in the depressed patients. We have 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 receptor-coupled Gs protein function may reflect reduced levels of the beta-adrenergic receptor previously shown in leukocytes of depressed patients; however, our complementary immunoblot studies suggest a direct, postreceptor, quantitative, and functional reduction in Gs protein in MNL of depressed patients.
通过霍乱毒素敏感的、异丙肾上腺素诱导的单核白细胞（MNL）对3H-Gpp(NH)p结合能力的增加，对26名抑郁症患者的β-肾上腺素能受体偶联Gs蛋白功能进行了测量。在抑郁症患者中观察到受体偶联Gs蛋白功能显著降低：鸟嘌呤核苷酸结合能力增加2.0±1.3%，而对照组为28.3±6.9%。单相和双相抑郁症患者均检测到类似的Gs蛋白功能降低。发现受体偶联Gs蛋白测量值与抑郁严重程度之间存在显著负相关。通过使用针对Gsα亚基的多克隆抗体进行免疫印迹分析，对MNL Gsα进行半定量测量，发现Gsα相对免疫反应性从对照组受试者的100±2.0%降至抑郁症患者的75.9±2.3%。我们之前曾描述过躁狂症患者白细胞中Gs蛋白功能亢进。目前抑郁症患者Gs功能降低的发现表明，受体偶联Gs蛋白活性是情感状态的生化指标。受体偶联Gs蛋白功能降低可能反映了抑郁症患者白细胞中先前显示的β-肾上腺素能受体水平降低；然而，我们的补充免疫印迹研究表明，抑郁症患者MNL中Gs蛋白存在直接的、受体后、定量和功能性降低。
