Lithium chloride inhibits thrombin-induced intracellular calcium mobilization in C6 rat glioma cells

1. 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. 2. 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. 3. On the other hand, pretreatment of the cells with 10 mM LiCl for 24 hr did not alter the amount of Gαq/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. 4. 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. 5. These results indicate that pretreatment with LiCl attenuated thrombin-evoked intracellular Ca²⁺ mobilization in plasmin sensitive manner in C6 rat glioma cells. 6. 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.