Amitriptyline modulated Ca2+ signaling and induced Ca2+-independent cell viability in human osteosarcoma cells
2018
Amitriptyline is a widely used tricyclic antidepressant, which acts primarily as a serotonin–norepinephrine reuptake inhibitor. This study examined the effect of amitriptyline on Ca2+ homeostasis and its related mechanism in MG63 human osteosarcoma cells. Amitriptyline evoked cytosolic-free Ca2+ concentrations ([Ca2+]i) rises concentration dependently. Amitriptyline-evoked Ca2+ entry was confirmed by Mn2+-induced quench of fura-2 fluorescence. This entry was inhibited by Ca2+ entry modulators nifedipine, econazole, SKF96365, the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate but was not affected by the PKC inhibitor GF109203X. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (TG) inhibited amitriptyline-evoked [Ca2+]i rises by 95%. Conversely, treatment with amitriptyline abolished TG-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 inhibited amitriptyline-evoked [Ca2+]i rises by 70%. Amitriptyline killed cells at 200–500...
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