Clomiphene, an ovulation-inducing agent, causes [Ca 2+ ] i increases in human osteoblast-like cells

Yu Chih Chen, Jue Long Wang, Chun Peng Liu, Jin Shiung Cheng, Hong Tai Chang, Yuk Keung Lo, Warren Su, Yee Ping Law, Wei Chung Chen, Chung Ren Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

15 Scopus citations

Abstract

The effect of clomiphene, an ovulation-inducing agent, on cytosolic free Ca 2+ levels ([Ca 2+ ] i ) in MG63 human osteosarcoma cells was explored by using fura-2 as a Ca 2+ indicator. Clomiphene at concentrations between 5-75 μM increased [Ca 2+ ] i in a concentration-dependent manner with an EC 50 of 50 μM. The [Ca 2+ ] i signal consisted of an initial rise and a sustained phase. Ca 2+ removal reduced the Ca 2+ signal by 40±10%. The [Ca 2+ ] i increase induced by 50 μM clomiphene was inhibited by 80±5% by 10 μM nifedipine, but was insensitive to 50 μM La 3+ or 10 μM verapamil. In Ca 2+ -free medium, pretreatment with 50 μM brefeldin A (to disrupt the Golgi complex Ca 2+ store), 1 μM thapsigargin (to inhibit the endoplasmic reticulum Ca 2+ pump), and carbonylcyanide m-chlorophenylhydrazone (CCCP; to uncouple mitochondria) inhibited 51±3% of 50 μM clomiphene-induced Ca 2+ release; conversely, pretreatment with 50 μM clomiphene abolished the [Ca 2+ ] i increase induced by thapsigargin, CCCP, and brefeldin A. The Ca 2+ release-induced by 50 μM clomiphene was unchanged by inhibition of phospholipase C with 2 μM 1-(6-((17β-3-methoxyestra-1,3,5 (10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). Collectively, the results suggest that clomiphene increased [Ca 2+ ] i in osteoblast-like cells, by releasing intracellular Ca 2+ in a phospholipase C-independent manner and by causing nifedipine-sensitive Ca 2+ influx.

Original languageEnglish
Pages (from-to)67-72
Number of pages6
JournalChinese Journal of Physiology
Volume44
Issue number2
StatePublished - 30 06 2001
Externally publishedYes

Keywords

  • Ca signaling
  • Clomiphene
  • Fura-2
  • MG63 cells
  • Osteoblasts

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