PMID- 29233021
OWN - NLM
STAT- MEDLINE
DCOM- 20180918
LR  - 20180918
IS  - 1477-0903 (Electronic)
IS  - 0960-3271 (Linking)
VI  - 37
IP  - 2
DP  - 2018 Feb
TI  - Amitriptyline modulated Ca(2+) signaling and induced Ca(2+)-independent cell 
      viability in human osteosarcoma cells.
PG  - 125-134
LID - 10.1177/0960327117693070 [doi]
AB  - Amitriptyline is a widely used tricyclic antidepressant, which acts primarily as 
      a serotonin-norepinephrine reuptake inhibitor. This study examined the effect of 
      amitriptyline on Ca(2+) homeostasis and its related mechanism in MG63 human 
      osteosarcoma cells. Amitriptyline evoked cytosolic-free Ca(2+) concentrations 
      ([Ca(2+)](i)) rises concentration dependently. Amitriptyline-evoked Ca(2+) entry 
      was confirmed by Mn(2+)-induced quench of fura-2 fluorescence. This entry was 
      inhibited by Ca(2+) 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 Ca(2+)-free medium, treatment with the 
      endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) inhibited 
      amitriptyline-evoked [Ca(2+)](i) rises by 95%. Conversely, treatment with 
      amitriptyline abolished TG-evoked [Ca(2+)](i) rises. Inhibition of phospholipase 
      C (PLC) with U73122 inhibited amitriptyline-evoked [Ca(2+)](i) rises by 70%. 
      Amitriptyline killed cells at 200-500 muM in a concentration-dependent fashion. 
      Chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane- N, N, N', 
      N'-tetraacetic acid/AM did not reverse amitriptyline-induced cytotoxicity. 
      Collectively, our data suggest that in MG63 cells, amitriptyline induced 
      [Ca(2+)](i) rises by evoking PLC-dependent Ca(2+) release from the endoplasmic 
      reticulum and Ca(2+) entry via PKC-regulated store-operated Ca(2+) entry. 
      Amitriptyline also induced Ca(2+)-disassociated cell death.
FAU - Lu, T
AU  - Lu T
AD  - 1 Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, 
      Taiwan.
FAU - Chou, C-T
AU  - Chou CT
AD  - 2 Department of Nursing, Division of Basic Medical Sciences, Chang Gung 
      University of Science and Technology, Chia-Yi, Taiwan.
AD  - 3 Chronic Diseases and Health Promotion Research Center, Chang Gung University of 
      Science and Technology, Chia-Yi, Taiwan.
FAU - Liang, W-Z
AU  - Liang WZ
AD  - 4 Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung, Taiwan.
FAU - Kuo, C-C
AU  - Kuo CC
AD  - 5 Department of Nursing, Tzu Hui Institute of Technology, Pingtung, Taiwan.
FAU - Chen, I-L
AU  - Chen IL
AD  - 6 Department of Pharmacy, Tajen University, Pingtung, Taiwan.
FAU - Wang, J-L
AU  - Wang JL
AD  - 7 Department of Rehabilitation, Kaohsiung Veterans General Hospital Tainan 
      Branch, Tainan, Taiwan.
FAU - Jan, C-R
AU  - Jan CR
AD  - 4 Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20170220
PL  - England
TA  - Hum Exp Toxicol
JT  - Human & experimental toxicology
JID - 9004560
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - 1806D8D52K (Amitriptyline)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amitriptyline/*toxicity
MH  - Antidepressive Agents, Tricyclic/*toxicity
MH  - Bone Neoplasms/*metabolism/pathology
MH  - Calcium/*metabolism
MH  - Calcium Signaling/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Endoplasmic Reticulum/drug effects/metabolism
MH  - Humans
MH  - Osteosarcoma/*metabolism/pathology
MH  - Protein Kinase C/metabolism
MH  - Time Factors
MH  - Type C Phospholipases/metabolism
OTO - NOTNLM
OT  - Amitriptyline
OT  - Ca2+
OT  - cytotoxicity
OT  - endoplasmic reticulum
OT  - human osteosarcoma cells
EDAT- 2017/12/14 06:00
MHDA- 2018/09/19 06:00
CRDT- 2017/12/14 06:00
PHST- 2017/12/14 06:00 [pubmed]
PHST- 2018/09/19 06:00 [medline]
PHST- 2017/12/14 06:00 [entrez]
AID - 10.1177/0960327117693070 [doi]
PST - ppublish
SO  - Hum Exp Toxicol. 2018 Feb;37(2):125-134. doi: 10.1177/0960327117693070. Epub 2017 
      Feb 20.