Effect of the neuroprotective agent riluzole on intracellular Ca2+ levels in IMR32 neuroblastoma cells.
Riluzole is an effective neuroprotective drug. Its effect on intracellular free Ca2+ levels ([Ca2+]i) has not been explored. This study examined the effect of riluzole on [Ca2+]i in IMR32 neuroblastoma cells using fura-2 as a Ca2+ probe. Riluzole 0.1-1 mM increased [Ca2+]i in a concentration-dependent manner. Removal of extracellular Ca2+ inhibited the response by 52 +/- 5%. The [Ca2+]i increase induced by 0.2 mM riluzole was unaltered by 0.1 mM La3+ or 10 microM verapamil, but was inhibited by 51 +/- 4% by 10 microM nifedipine. In Ca2+-free medium, pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) reduced the 0.2 mM riluzole-induced Ca2+ release by 44 +/- 3%; this reduction was augmented to 66 +/- 5% by additionally depleting the Ca2+ stores in the Golgi complex with 50 microM brefeldin A. Inhibition of inositol 1,4,5-trisphosphate formation by 2 microM U73122, a phospholipase C inhibitor, did not affect Ca2+ release induced by 0.2 microM riluzole. It was concluded that the neuroprotective agent riluzole increased [Ca2+]i in IMR32 neuroblastoma cells concentration-dependently by releasing Ca2+ from multiple stores in an inositol 1,4,5-trisphosphate-independent manner and also by inducing nifedipine-sensitive Ca2+ influx.
Wang
J L
JL
Department of Rehabilitation, Kaohsiung Veterans General Hospital, Taiwan.
Lee
K C
KC
Tang
K Y
KY
Lu
T
T
Chang
C H
CH
Chow
C K
CK
Chen
W C
WC
Su
W
W
Law
Y P
YP
Jan
C R
CR
D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016257:Fura-2 / Q000493:pharmacokinetics; D005910:Glioma; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008113:Liver Neoplasms; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019782:Riluzole / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007476:Ionophores; D018696:Neuroprotective Agents; D011500:Protein Synthesis Inhibitors; D020126:Brefeldin A; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D019284:Thapsigargin; D019782:Riluzole; D002118:Calcium; D016257:Fura-2