Kawamoto H, Watanabe Y, Imaizumi T, Iwasaki T, Yoshida H
Department of Medicine I, Hyogo College of Medicine, Japan.
Eur J Pharmacol. 1991 Jan 25;206(1):33-7. doi: 10.1016/0922-4106(91)90143-6.
Studies were made on the effects of Li+ on ADP ribosylation of inhibitory GTP-binding (Gi) protein by islet-activating protein (IAP), pertussis toxin. The ADP ribosylation of 40-41 kDa proteins of the membranes of rat cardiac ventricular cells by IAP was reduced by the addition of a nonhydrolyzable analog of guanine nucleotide, GTP gamma S, indicating that these proteins included Gi protein. The addition of LiCl (0.5-10 mM) to the membrane fractions of the cells attenuated the ADP ribosylation of the Gi protein of the cell membranes by IAP dose-dependently. The effects of LiCl were reversible. Of the monovalent ions tested, Li+ inhibited the ADP ribosylation of the protein by IAP most strongly. The effects of LiCl (2 mM) were observed even in the presence of 150 mM KCl. Moreover, LiCl decreased the ADP ribosylation of purified Gi protein by IAP. These results support that Gi proteins are one of the targets for the therapeutic effects of lithium.
开展了关于锂离子对胰岛激活蛋白（IAP）即百日咳毒素介导的抑制性GTP结合蛋白（Gi）的ADP核糖基化作用的研究。添加鸟嘌呤核苷酸的非水解类似物GTPγS可降低IAP对大鼠心室肌细胞膜40 - 41 kDa蛋白的ADP核糖基化作用，这表明这些蛋白包含Gi蛋白。向细胞的膜组分中添加LiCl（0.5 - 10 mM）可剂量依赖性地减弱IAP对细胞膜Gi蛋白的ADP核糖基化作用。LiCl的作用是可逆的。在所测试的单价离子中，Li +对IAP介导的蛋白ADP核糖基化作用的抑制最为强烈。即使存在150 mM KCl，仍可观察到2 mM LiCl的作用。此外，LiCl可降低IAP对纯化的Gi蛋白的ADP核糖基化作用。这些结果支持Gi蛋白是锂治疗作用的靶点之一。
