一种新的钙传感器刺激肌醇磷酸形成和GCT23破骨细胞样细胞表达的[Ca2+]i信号。

K Seuwen, H G Boddeke, S Migliaccio, M Perez, A Taranta, A Teti
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引用次数: 35

摘要

[Ca2+]o升高可抑制破骨细胞活性;然而,潜在的分子机制尚不清楚。我们使用人破骨细胞样细胞GCT23来阐明它们的阳离子感知特性。细胞对升高的[Ca2+]o的反应是快速的浓度依赖性[Ca2+]i瞬变(EC50 = 7.8 mm,峰值时间为44 +/- 4秒),这是由于细胞内储存的释放,然后是Ca2+在质膜上的内流。Ca2+储存耗竭由thapsigargin,内皮素-1,或缓激素激活钙进入途径。细胞对Ni2+和Cd2+的反应相似,但动力学较慢(EC50)
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A novel calcium sensor stimulating inositol phosphate formation and [Ca2+]i signaling expressed by GCT23 osteoclast-like cells.

Osteoclast activity is inhibited by elevated [Ca2+]o; however, the underlying molecular mechanism is unknown. We used the human osteoclast-like cells GCT23 to elucidate their cation-sensing properties. Cells responded to elevated [Ca2+]o with rapid concentration-dependent [Ca2+]i transients (EC50 = 7.8 mm, time to peak 44 +/- 4 sec) that were due to release from intracellular stores, followed by Ca2+ influx across the plasma membrane. Ca2+ store depletion by thapsigargin, endothelin-1, or bradykinin activated calcium entry pathways. Cells responded similarly to Ni2+ and Cd2+ with albeit slower kinetics (EC50 <10 microm and <100 microm, times to peak 140 +/- 25 sec and 150 +/- 24 sec, respectively). The three cations stimulated inositol phosphate production (two-fold, p <.02) similar to bradykinin (2.5-fold, p <. 002), which activates a phospholipase C (PLC)-coupled receptor in GCT23 cells. The cells did not respond to 0.1-1 mM Gd3+ or neomycin B, indicating that the parathyroid calcium receptor (PCaR) is not functionally expressed. In confirmation, PCaR could not be detected by reverse transcriptase polymerase chain reaction in GCT23 cells and in mouse osteoclasts, and the calcimimetic compound NPS R-568 failed to produce the left shift of the concentration-response curve characteristic for PCaR. Our data demonstrate for the first time that cation sensing by osteoclast-like GCT23 cells is mediated by a PLC-coupled receptor that is not identical to PCaR.

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