Avissar S, Barki-Harrington L, Herishanu Y, Schreiber G
Department of Clinical Pharmacology, Faculty for Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Mov Disord. 1997 Mar;12(2):167-74. doi: 10.1002/mds.870120206.
Early events in signal information transduction beyond dopamine, beta-adrenergic, and muscarinic receptors, involving receptor-coupled G-protein function and G alpha subunit immunoreactive levels were measured in mononuclear leukocytes (MNLs) of 12 never-treated patients with Parkinson's disease in comparison with 10 age- and sex-matched healthy control subjects. Both beta-adrenergic and dopamine receptor-coupled Gs protein function as measured by cholera toxin-sensitive, isoproterenol- and dopamine-induced increases in Gpp(NH)p-binding capacity, in MNLs of patients with Parkinson's disease were found to be significantly reduced in comparison with those in the control group. Muscarinic receptor-coupled non-Gs (Gi or G(o)) protein function: pertussis toxin-sensitive, carbamylcholine-induced increase in Gpp(NH)p-binding capacity, was not found to be significantly different between patients with Parkinson's disease and control subjects. G protein alpha subunits were measured through immunoblotting analyses with specific polyclonal antibodies against G alpha s, G alpha i, and G alpha q subunits. MNL levels of the 45-kDa species of G alpha s were found to be significantly reduced in patients with Parkinson's disease in comparison with control subjects. Other non-Gs proteins (Gi, Gq) did not show any significant quantitative differences between patients with Parkinson's disease and control subjects. The reductions in G alpha s levels in MNLs of patients with Parkinson's disease may explain the beta-adrenergic and dopamine receptor-coupled Gs protein hypofunction detected in MNLs of these patients. As previous studies have failed to observe significant changes in receptor levels in MNLs of patients with Parkinson's disease, our findings of reduced dopaminergic and beta-adrenergic receptor-coupled Gs function and of G alpha s immunoreactive levels in MNLs of Parkinson's patients point to alterations distal to these receptors at the level of the signal-transducing Gs protein.
在12例未经治疗的帕金森病患者的单核白细胞（MNLs）中，测量了除多巴胺、β-肾上腺素能和毒蕈碱受体之外的信号信息转导早期事件，这些事件涉及受体偶联G蛋白功能和Gα亚基免疫反应水平，并与10名年龄和性别匹配的健康对照受试者进行了比较。通过霍乱毒素敏感的异丙肾上腺素和多巴胺诱导的Gpp(NH)p结合能力增加来测量，发现帕金森病患者MNLs中β-肾上腺素能和多巴胺受体偶联的Gs蛋白功能与对照组相比显著降低。毒蕈碱受体偶联的非Gs（Gi或G(o)）蛋白功能：百日咳毒素敏感的氨甲酰胆碱诱导的Gpp(NH)p结合能力增加，在帕金森病患者和对照受试者之间未发现显著差异。通过用针对Gαs、Gαi和Gαq亚基的特异性多克隆抗体进行免疫印迹分析来测量G蛋白α亚基。与对照受试者相比，帕金森病患者中45 kDa的Gαs物种的MNL水平显著降低。其他非Gs蛋白（Gi、Gq）在帕金森病患者和对照受试者之间未显示任何显著的定量差异。帕金森病患者MNLs中Gαs水平的降低可能解释了在这些患者MNLs中检测到的β-肾上腺素能和多巴胺受体偶联的Gs蛋白功能低下。由于先前的研究未能观察到帕金森病患者MNLs中受体水平的显著变化，我们在帕金森病患者MNLs中发现多巴胺能和β-肾上腺素能受体偶联的Gs功能降低以及Gαs免疫反应水平降低，这表明在信号转导Gs蛋白水平上这些受体远端存在改变。
