Lithium chloride inhibits thrombin-induced intracellular calcium mobilization in C6 rat glioma cells.
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.
Kagaya
A
A
Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Japan. kagaya@ue.ipc.hiroshima-u.ac.jp
Okada
A
A
Tawara
Y
Y
Inagaki
M
M
Jitsuiki
H
H
Kozuru
T
T
Miyoshi
I
I
Katagiri
H
H
Uchitomi
Y
Y
Horiguchi
J
J
Nakata
Y
Y
Yamawaki
S
S
D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005341:Fibrinolysin / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology*; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D005343:Fibrinolytic Agents; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012701:Serotonin; D013917:Thrombin; D005341:Fibrinolysin; D018021:Lithium Chloride; D002118:Calcium