A zinc-sensing receptor triggers the release of intracellular Ca2+ and regulates ion transport
A zinc-sensing receptor triggers the release of intracellular Ca2+ and regulates ion transport
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DOI：
10.1073/pnas.201193398
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发表时间：
2001-09-25
影响因子：
11.1
通讯作者：
Sekler, I
中科院分区：
文献类型：
--
作者：
Hershfinkel, M;Moran, A;Sekler, I
细胞外锌浓度的变化参与调节基本的细胞过程，如增殖，分泌和离子转运的机制还不清楚。在这里，我们表明微摩尔浓度的细胞外锌会引发结肠细胞系HT 29中毒胡萝卜素敏感的细胞内池中大量释放钙。钙释放被磷脂酶-C抑制剂阻断，表明形成肌醇1，4，5-三磷酸是锌依赖性钙释放所必需的。未观察到锌内流，表明细胞外锌触发释放。Ca ~（2+）的释放是锌特异性的，其它重金属不能触发Ca ~（2+）的释放。此外，锌不能激活HEK 293细胞中异源表达的Ca 2+敏感受体。锌诱导的Ca ~（2+）升高可刺激HT 29细胞Na ~+/H ~+交换活性。我们的研究结果表明，以前未表征的细胞外，G蛋白偶联，锌离子敏感受体在结肠细胞中的功能。由于已知Ca 2+升高调节关键的细胞和信号转导过程，锌敏感受体可能提供细胞外锌浓度变化和细胞过程调节之间缺失的环节。
Changes in extracellular zinc concentration participate in modulating fundamental cellular processes such as proliferation, secretion, and ion transport in a mechanism that is not well understood. Here, we show that a micromolar concentration of extracellular zinc triggers a massive release of calcium from thapsigargin-sensitive intracellular pools in the colonocytic cell line HT29. Calcium release was blocked by a phospholipase-C inhibitor, indicating that formation of inositol 1,4,5-triphosphate is required for zinc-dependent calcium release. Zinc influx was not observed, indicating that extracellular zinc triggered the release. The Ca-i(2+) release was zinc specific and could not be triggered by other heavy metals. Furthermore, zinc failed to activate the Ca2+-sensing receptor heterologously expressed in HEK293 cells. The zinc-induced Ca-i(2+) rise stimulated the activity of the Na+/H+ exchanger in HT29 cells. Our results indicate that a previously uncharacterized extracellular, G protein-coupled, Zn2+-sensing receptor is functional in colonocytes. Because Ca-i(2+) rise is known to regulate key cellular and signal-transduction processes, the zinc-sensing receptor may provide the missing link between extracellular zinc concentration changes and the regulation of cellular processes.