Watanabe Y, Kawamoto H, Imaizumi T, Sakagoshi N, Iwakura K, Morita H, Iwasaki T, Yoshida H
Department of Pharmacology I, Osaka University, School of Medicine, Japan.
Cell Signal. 1991;3(1):59-64. doi: 10.1016/0898-6568(91)90008-i.
Addition of lithium ion to the inhibitory GTP-binding (Gi) protein resulted in a decrease of its ADP-ribosylation by islet-activating protein (pertussis toxin, IAP). The possibility that this decrease was due to dissociation of the Gi protein trimer was examined. Results showed that lithium ions had no appreciable effect on either the Gi protein trimer or its dissociation into its three subunits induced by Mg2+ and GTP gamma S. Next, the effect of lithium ions on Gi protein-mediated adenylate cyclase inhibition and alpha 2-adrenoceptor in human platelet membranes was examined. Lithium ion was found to impair adenylate cyclase inhibition of alpha 2-adrenoceptor stimulation of forskolin-stimulated enzyme activities. The monovalent ion also abolished guanine nucleotide modulation (GTP shift) of agonist binding, while it had no remarkable effects on antagonist binding in alpha 2-adrenoceptor of human platelet membranes. These results suggested that lithium ion caused functional change of the Gi protein without remarkable change of its dissociation, causing modulation in a coupling between alpha 2-adrenoceptor and Gi protein.
向抑制性GTP结合蛋白（Gi蛋白）中添加锂离子会导致其被胰岛激活蛋白（百日咳毒素，IAP）进行ADP核糖基化的程度降低。研究了这种降低是否是由于Gi蛋白三聚体解离所致。结果表明，锂离子对Gi蛋白三聚体或其在Mg2+和GTPγS诱导下解离成三个亚基均无明显影响。接下来，研究了锂离子对人血小板膜中Gi蛋白介导的腺苷酸环化酶抑制作用和α2肾上腺素能受体的影响。发现锂离子会损害α2肾上腺素能受体刺激福斯高林刺激的酶活性时对腺苷酸环化酶的抑制作用。该单价离子还消除了激动剂结合的鸟嘌呤核苷酸调节（GTP位移），而对人血小板膜α2肾上腺素能受体中的拮抗剂结合没有显著影响。这些结果表明，锂离子引起了Gi蛋白的功能变化，而其解离没有明显变化，从而导致α2肾上腺素能受体与Gi蛋白之间的偶联发生调节。
