Schreiber G, Avissar S
Department of Psychiatry, Faculty for Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Isr Med Assoc J. 2000 Jul;2 Suppl:86-91.
There is a significant gap between advances in medication for mental disorders and the present static situation of diagnosis and monitoring treatments of these disorders. Heterotrimeric G proteins play a pivotal role in postreceptor information transduction. These proteins were previously implicated by us in the biochemical mechanism underlying lithium action, and in the pathophysiology of mood disorders. We aimed at quantitatively and functionally evaluating G proteins in patients with major mental disorders in an attempt to unravel a differential pattern of G protein measures characterizing each disorder. We undertook G protein functional measurements coupled to beta-adrenergic, muscarinic or dopamine receptors through bacterial toxin-sensitive, agonist-enhanced [3H]-Gpp(NH)p binding capacity, substituted by quantitative measures of G alpha s, G alpha i, and G beta subunit proteins through immunoblot analysis using polyclonal anti-G submit antibodies in mononuclear leukocytes obtained from patients with major mental disorders in comparison with healthy volunteers. A differential pattern of receptor coupled G protein function and of their immunoreactive levels were detected in mononuclear leukocytes of patient s for the following mental disorders: mania, depression, schizophrenia, and panic. Normalization of altered G protein measures in mood-disorder ed patients occurred under specific treatments. As state-dependent markers, G protein measures can potentially be used as an aid in both the biochemical diagnosis of mental disorders and in the biochemical monitoring of the response to a specific treatment.
精神障碍药物治疗的进展与目前这些障碍的诊断和治疗监测的静止状态之间存在显著差距。异三聚体G蛋白在受体后信息转导中起关键作用。我们之前发现这些蛋白参与锂作用的生化机制以及情绪障碍的病理生理学。我们旨在对重度精神障碍患者的G蛋白进行定量和功能评估，以试图揭示表征每种障碍的G蛋白测量的差异模式。我们通过细菌毒素敏感、激动剂增强的[3H]-Gpp(NH)p结合能力，对与β-肾上腺素能、毒蕈碱或多巴胺受体偶联的G蛋白进行功能测量，并用多克隆抗G亚基抗体通过免疫印迹分析对Gαs、Gαi和Gβ亚基蛋白进行定量测量，这些测量是在从重度精神障碍患者与健康志愿者获取的单核白细胞中进行的。在以下精神障碍患者的单核白细胞中检测到受体偶联G蛋白功能及其免疫反应水平的差异模式：躁狂症、抑郁症、精神分裂症和恐慌症。情绪障碍患者中改变的G蛋白测量在特定治疗下恢复正常。作为状态依赖性标志物，G蛋白测量有可能用于精神障碍的生化诊断以及对特定治疗反应的生化监测。
