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• W2051539069 abstract "Riluzole is a drug used in the treatment of amyotrophic lateral sclerosis; however, its in vitro action is unclear. In this study, the effect of riluzole on intracellular Ca 2 - concentration ([Ca 2 - ] i ) in Madin-Darby canine kidney (MDCK) cells was investigated using the Ca 2 - -sensitive fluorescent dye, fura-2. Riluzole (100 -500 mM) caused a rapid and sustained increase of [Ca 2 - ] i in a concentration-dependent manner (EC 50 = 150 mM). Some 40 and 50% of this [Ca 2 - ] i increase was prevented by the removal of extracellular Ca 2 - and the addition of La 3 - , respectively, but was unchanged by dihydropyridines, verapamil and diltiazem. In Ca 2 - -free medium, thapsigargin -an inhibitor of the endoplasmic reticulum (ER) Ca 2 - -ATPase -caused a monophasic [Ca2-] i increase, after which the increasing effect of riluzole on [Ca 2 - ] i was attenuated by 70%; in addition, pre-treatment with riluzole abolished thapsigargin-induced [Ca 2 - ] i increases. U73122, an inhibitor of phospholipase C (PLC), abolished ATP (but not riluzole)-induced [Ca 2 - ] i increases. At concentrations of 250 and 500 mM, riluzole killed 40 and 95% cells, respectively. The cytotoxic effect of riluzole (250 mM) was unaltered by pre-chelating cytosolic Ca 2 - with BAPTA. Collectively, in MDCK cells, riluzole rapidly increased [Ca 2 - ] i by stimulating extra-cellular Ca 2 - influx via an La 3 - -sensitive pathway and intracellular Ca 2 - release from the ER via, as yet, unidentified mechanisms. Furthermore, riluzole caused Ca 2 - -unrelated cytotoxicity in a concentration-depen-dent manner." @default.
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• W2051539069 date "2006-08-01" @default.
• W2051539069 modified "2023-10-16" @default.
• W2051539069 title "Effect of Riluzole on Ca2+ Movement and Cytotoxicity in Madin-Darby Canine Kidney Cells" @default.
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• W2051539069 doi "https://doi.org/10.1191/0960327106het641oa" @default.
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