Abstract
The extracellular calcium-sensing receptor (CaSR) is activated by divalent cations and might mediate some of the effects of strontium ranelate, a new drug for the prevention and treatment of post-menopausal osteoporosis. Here, we showed that the maximal effect of Sr 2+ was comparable to that observed for Ca 2+ for both the cloned rat CaSR expressed in Chinese hamster ovary [CHO(CaSR)] cells and the mouse CaSR constitutively expressed in AtT-20 cells as measured by the accumulation of [ 3H]inositol phosphates (IP) resulting from CaSR activation. Strontium ranelate also displayed comparable agonist activity for the CaSR in both cell lines. Sodium ranelate did not stimulate the IP response in CHO(CaSR) cells. The IP response resulting from activation of other G-protein-coupled receptors was potentiated by Sr 2+, suggesting that entry of Sr 2+ into the cells might influence phospholipase C activity. Modulation of the CaSR activity in bone cells by strontium ranelate may contribute to its reported antiosteoporotic effects.
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