Kagaya A, Okada A, Tawara Y, Inagaki M, Jitsuiki H, Kozuru T, Miyoshi I, Katagiri H, Uchitomi Y, Horiguchi J, Nakata Y, Yamawaki S
Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Japan.
Prog Neuropsychopharmacol Biol Psychiatry. 2000 Jan;24(1):85-95. doi: 10.1016/s0278-5846(99)00082-2.
In this study, the authors have demonstrated the effect of lithium, a typical mood stabilizer, on thrombin-evoked Ca2+ mobilization in C6 cells to elucidate the action mechanisms of the drug. Thrombin-induced Ca2 mobilization was reduced 24 hr after 1 or 10 mM lithium chloride (LiCl) pretreatment. The Ca2+ rise was reduced in a time-dependent manner, and the significant inhibition was observed 9 hr pretreatment with 10 mM LiCl. On the other hand, pretreatment of the cells with 10 mM LiCl for 24 hr did not alter the amount of Galphaq/11 significantly. Pretreatment with 10 mM LiCl for 24 hr failed to reduce the 5-HT-induced Ca2+ mobilization or to affect the desensitization of the 5-HT signal. Finally, thrombin-elicited Ca2+ rise was markedly inhibited in the presence of 0.05 U/ml plasmin, however, the Ca2+ rise was not further attenuated in the presence of plasmin in C6 cells pretreated with LiCl for 24 hr. These results indicate that pretreatment with LiCl attenuated thrombin-evoked intracellular Ca2+ mobilization in plasmin sensitive manner in C6 rat glioma cells. Thus, it is important to investigate the effect of lithium on thrombin-induced cellular responses to clarify the action mechanism of lithium in relation to some abnormality in thrombin-evoked Ca2+ rise observed in bipolar disorders.
在本研究中，作者展示了典型心境稳定剂锂对C6细胞中凝血酶诱发的Ca2+动员的影响，以阐明该药物的作用机制。在1或10 mM氯化锂（LiCl）预处理24小时后，凝血酶诱导的Ca2+动员减少。Ca2+升高呈时间依赖性降低，在10 mM LiCl预处理9小时时观察到显著抑制。另一方面，用10 mM LiCl预处理细胞24小时并未显著改变Galphaq/11的量。用10 mM LiCl预处理24小时未能降低5-羟色胺（5-HT）诱导的Ca2+动员，也未影响5-HT信号的脱敏。最后，在存在0.05 U/ml纤溶酶的情况下，凝血酶引发的Ca2+升高受到显著抑制，然而，在用LiCl预处理24小时的C6细胞中，在存在纤溶酶的情况下Ca2+升高并未进一步减弱。这些结果表明，LiCl预处理以纤溶酶敏感的方式减弱了C6大鼠胶质瘤细胞中凝血酶诱发的细胞内Ca2+动员。因此，研究锂对凝血酶诱导的细胞反应的影响，以阐明锂与双相情感障碍中观察到的凝血酶诱发的Ca2+升高异常相关的作用机制非常重要。
