Effect of riluzole on cytosolic Ca2+ increase in human osteosarcoma cells.
In human osteosarcoma MG63 cells, the effect of the neuroprotective drug riluzole on the intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured using fura-2. Riluzole (50-500 micromol/l) caused a rapid and sustained plateau increase in [Ca(2+)](i) in a concentration-dependent manner (EC(50) = 150 micromol/l). The riluzole-induced rise in [Ca(2+)](i) was prevented by 58 and 20% by extracellular Ca(2+) removal and nifedipine, respectively, but was not changed by La(3+) and verapamil. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum (ER) Ca(2+)-ATPase, caused a monophasic increase in [Ca(2+)](i), after which the increasing effect of riluzole on [Ca(2+)](i) was attenuated by 84%; also, pretreatment with riluzole abolished the thapsigargin-induced [Ca(2+)](i) increase. U73122, an inhibitor of phospholipase C, abrogated the ATP (but not riluzole)-induced rise in [Ca(2+)](i). A low concentration (6 micromol/l) of riluzole selectively potentiated the bradykinin (but not ATP and histamine)-induced increase in [Ca(2+)](i). These results suggest that riluzole rapidly increases [Ca(2+)](i) by stimulating both the extracellular Ca(2+) influx via a nifedipine-sensitive pathway and intracellular Ca(2+) release from the ER via an as yet unidentified mechanism(s).
Jan
Chung-Ren
CR
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. crjan@isca.vghks.gov.tw
Lu
Yih-Chau
YC
Jiann
Bang-Ping
BP
Chang
Hong-Tai
HT
Huang
Jong-Khing
JK
D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism*; D019782:Riluzole / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D019782:Riluzole; D002118:Calcium