Effect of maprotiline on Ca(2+) movement in human neuroblastoma cells.
In human neuroblastoma IMR32 cells, the effect of the anti-depressant maprotiline on baseline intracellular Ca2+ concentrations ([Ca2+]i) was explored by using the Ca2+-sensitive probe fura-2. Maprotiline at concentrations greater than 100 microM caused a rapid rise in [Ca2+]i in a concentration-dependent manner (EC50 = 200 microM). Maprotiline-induced [Ca2+]i rise was reduced by 50% by removal of extracellular Ca2+. Maprotiline-induced [Ca2+]i rises were inhibited by half by nifedipine, but was unaffected by verapamil or diiltiazem. In Ca2+-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-ATPase, caused a monophasic [Ca2+]i rise, after which the increasing effect of maprotiline on [Ca2+]i was abolished. U73122, an inhibitor of phospholipase C, did not affect maprotiline-induced [Ca2+]i rises. These findings suggest that in human neuroblastoma cells, maprotiline increases [Ca2+]i by stimulating extracellular Ca2+ influx and also by causing intracellular Ca2+ release from the endoplasmic reticulum via a phospholiase C-independent manner.
Hsu
Shu-Shong
SS
Department of Surgery, Ping Tung Christian Hospital, Ping Tung 900, Taiwan.
Chen
Wei-Chuan
WC
Lo
Yuk-Keung
YK
Cheng
Jin-Shiung
JS
Yeh
Jeng-Hsien
JH
Cheng
He-Hsing
HH
Chen
Jin-Shyr
JS
Chang
Hong-Tai
HT
Jiann
Bang-Ping
BP
Huang
Jong-Khing
JK
Jan
Chung-Ren
CR
D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016257:Fura-2 / Q000378:metabolism; D006801:Humans; D008376:Maprotiline / Q000493:pharmacokinetics* / Q000494:pharmacology*; D009543:Nifedipine / Q000378:metabolism; D019284:Thapsigargin / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism; D014700:Verapamil / Q000378:metabolism
D002121:Calcium Channel Blockers; D008376:Maprotiline; D019284:Thapsigargin; D014700:Verapamil; D010738:Type C Phospholipases; D009543:Nifedipine; D002118:Calcium; D016257:Fura-2