The effects of the antidepressant mirtazapine on cytosolic Ca2+ concentrations ([Ca2+]i) in human prostate cancer PC3 cells and human osteosarcoma MG63 cells were measured by Ca2+-sensitive fluorescent probe fura-2. In Ca2+-containing medium, mirtazapine induced [Ca2+]i rises in a concentration-dependent manner in both PC3 and MG63 cells. Removal of extracellular Ca2+ inhibited the mirtazapine-induced Ca2+ signal. In Ca2+-free medium, thapsigargin (an inhibitor of the endoplasmic reticulum Ca2+-ATPase pump) induced [Ca2+]i rises by passively depleting the endoplasmic reticulum Ca2+ store, after which the increasing effect of mirtazapine (1.5 mM) on [Ca2+]i was reduced. Conversely, pretreatment with mirtazapine decreased thapsigargin-induced [Ca2+]i rises in PC3 and MG63 cells. When PC3 cells were pretreated with U73122, a phospholipase C inhibitor, mirtazapine-induced [Ca2+]i rises were inhibited by 47%. But in MG63 cells, 2 mM U73122 did not change mirtazapine-induced [Ca2+]i rises. These finding suggest that mirtazapine-induced [Ca2+]i rises were caused both by extracellular Ca2+ influx and intracellular depletion of the endoplasmic reticulum Ca2+ stores. Furthermore, the mechanism of mirtazapine-induced Ca2+ release may be different between PC3 and MG63 cells. Additionally, cell proliferation assays suggest that overnight incubation with higher concentrations of mirtazapine decreased cell viability in a concentration-dependent manner.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0712105-093142 |
| Date | 12 July 2005 |
| Creators | Pan, Chih-chuan |
| Contributors | Chen-fu Shaw, Chung-ren Jan, Hung-tu Huang, Jau-cheng Liou |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0712105-093142 |
| Rights | campus_withheld, Copyright information available at source archive |
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