The calcium-sensing receptor regulates calcium absorption in MDCK cells by inhibition of PMCA
The calcium-sensing receptor regulates calcium absorption in MDCK cells by inhibition of PMCA
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DOI：
10.1152/ajprenal.2001.280.5.f815
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发表时间：
2001-05-01
影响因子：
4.2
通讯作者：
Arthur, JM
中科院分区：
文献类型：
--
作者：
Blankenship, KA;Williams, JJ;Arthur, JM
通过钙敏感受体（CaR）激动剂刺激基底表面，测量了钙在Madin-Darby犬肾（MDCK）细胞单层上的转运。CaR的刺激导致钙转运的时间和浓度依赖性抑制，但不改变上皮电压或电阻。百日咳毒素预处理细胞对转运的抑制作用没有改变，但被磷脂酶C （PLC）抑制剂U-73122阻断。为了确定CaR抑制钙转运的潜在机制，我们测量了质膜钙atp酶（PMCA）的活性。刺激基底表面的CaR导致PMCA以浓度和plc依赖的方式受到抑制。因此，通过plc依赖途径刺激CaR抑制钙转运和PMCA活性。这些研究提供了第一个直接证据，证明钙可以在远端小管模型中抑制其自身的跨细胞吸收。此外，它们为CaR抑制钙转运，抑制PMCA提供了一种潜在的机制。
Calcium transport across a monolayer of Madin-Darby canine kidney (MDCK) cells was measured in response to stimulation of the basal surface with calcium-sensing receptor (CaR) agonists. Stimulation of the CaR resulted in a time- and concentration-dependent inhibition of calcium transport but did not change transepithelial voltage or resistance. Inhibition of transport was not altered by pretreatment of cells with pertussis toxin but was blocked by the phospholipase C (PLC) inhibitor U-73122. To determine a potential mechanism by which the CaR could inhibit calcium transport, we measured activity of the plasma membrane calcium ATPase (PMCA). Stimulation of the CaR on the basal surface resulted in an inhibition of the PMCA in a concentration-and PLC-dependent manner. Thus stimulation of the CaR inhibits both calcium transport and PMCA activity through a PLC-dependent pathway. These studies provide the first direct evidence that calcium can inhibit its own transcellular absorption in a model of the distal tubule. In addition, they provide a potential mechanism for the CaR to inhibit calcium transport, inhibition of PMCA.