• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Role of calcium channels in carboxyl-terminal parathyroid hormone receptor signaling.
【24h】

Role of calcium channels in carboxyl-terminal parathyroid hormone receptor signaling.

机译：钙通道在羧基末端甲状旁腺激素受体信号传导中的作用。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Parathyroid hormone (PTH), an 84-amino acid polypeptide, is a major systemic regulator of calcium homeostasis that activates PTH/PTHrP receptors (PTH1Rs) on target cells. Carboxyl fragments of PTH (CPTH), secreted by the parathyroids or generated by PTH proteolysis in the liver, circulate in blood at concentrations much higher than intact PTH-(1-84) but cannot activate PTH1Rs. Receptors specific for CPTH fragments (CPTHRs), distinct from PTH1Rs, are expressed by bone cells, especially osteocytes. Activation of CPTHRs was previously reported to modify intracellular calcium within chondrocytes. To further investigate the mechanism of action of CPTHRs in osteocytes, cytosolic free calcium concentration ([Ca(2+)](i)) was measured in the PTH1R-null osteocytic cell line OC59, which expresses abundant CPTHRs but no PTH1Rs. [Ca(2+)](i) was assessed by single-cell ratiometric microfluorimetry in fura-2-loaded OC59 cells. A rapid and transient increase in [Ca(2+)](i) was observed in OC59 cells in response to theCPTH fragment hPTH-(53-84) (250 nM). No [Ca(2+)](i) signal was observed in COS-7 cells, in which CPTHR binding also cannot be detected. Neither hPTH-(1-34) nor a mutant CPTH analog, [Ala(55-57)]hPTH-(53-84), that does not to bind to CPTHRs, increased [Ca(2+)](i) in OC59 cells. The [Ca(2+)](i) response to hPTH-(53-84) required the presence of extracellular calcium and was blocked by inhibitors of voltage-dependent calcium channels (VDCCs), including nifedipine (100 nM), omega-agatoxin IVA (10 nM), and omega-conotoxin GVIA (100 nM). We conclude that activation of CPTHRs in OC59 osteocytic cells leads to a rapid increase in influx of extracellular calcium, most likely through the opening of VDCCs.
机译：甲状旁腺激素（PTH）是一种84个氨基酸的多肽，是钙稳态的主要系统调节剂，可激活靶细胞上的PTH / PTHrP受体（PTH1Rs）。由甲状旁腺分泌的或由PTH蛋白水解在肝脏中产生的PTH的羧基片段（CPTH）在血液中循环的浓度远高于完整的PTH-（1-84），但不能激活PTH1Rs。不同于PTH1R的CPTH片段（CPTHRs）特异的受体由骨细胞，尤其是骨细胞表达。以前有报道称CPTHRs的激活会修饰软骨细胞内的细胞内钙。为了进一步研究CPTHRs在骨细胞中的作用机理，在表达大量CPTHRs但不表达PTH1Rs的PTH1R-null骨细胞系OC59中测量了胞浆游离钙浓度（[Ca（2 +）]（i））。 [Ca（2 +）]（i）是通过单细胞比例微荧光法在呋喃2加载的OC59细胞中评估的。响应CPTH片段hPTH-（53-84）（250 nM），在OC59细胞中观察到[Ca（2 +）]（i）的快速和短暂增加。在COS-7细胞中未观察到[Ca（2 +）]（i）信号，在该细胞中也无法检测到CPTHR结合。 hPTH-（1-34）或不与CPTHRs结合的突变CPTH类似物[Ala（55-57）] hPTH-（53-84）均未增加[Ca（2 +）]（i） OC59细胞。对hPTH-（53-84）的[Ca（2 +）]（i）响应需要细胞外钙的存在，并被电压依赖性钙通道（VDCC）抑制剂（包括硝苯地平（100 nM），欧米茄-琼脂毒素IVA（10 nM）和ω-芋螺毒素GVIA（100 nM）。我们得出的结论是，OC59骨细胞中CPTHRs的激活导致细胞外钙的流入迅速增加，这很可能是通过VDCCs的开放引起的。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号