title: Effect of maprotiline on Ca(2+) movement in human neuroblastoma cells.
abstract: 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.
authors.affiliation: Department of Surgery, Ping Tung Christian Hospital, Ping Tung 900, Taiwan.
authors.forename: Shu-Shong
authors.initials: SS
authors.lastname: Hsu
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Chen
authors.forename: Yuk-Keung
authors.initials: YK
authors.lastname: Lo
authors.forename: Jin-Shiung
authors.initials: JS
authors.lastname: Cheng
authors.forename: Jeng-Hsien
authors.initials: JH
authors.lastname: Yeh
authors.forename: He-Hsing
authors.initials: HH
authors.lastname: Cheng
authors.forename: Jin-Shyr
authors.initials: JS
authors.lastname: Chen
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: Bang-Ping
authors.initials: BP
authors.lastname: Jiann
authors.forename: Jong-Khing
authors.initials: JK
authors.lastname: Huang
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: 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
chemical_list: D002121:Calcium Channel Blockers; D008376:Maprotiline; D019284:Thapsigargin; D014700:Verapamil; D010738:Type C Phospholipases; D009543:Nifedipine; D002118:Calcium; D016257:Fura-2