高钙及其他二价阳离子可增加牛甲状旁腺细胞中的肌醇三磷酸。

High calcium and other divalent cations increase inositol trisphosphate in bovine parathyroid cells.

作者信息

Shoback D M, Membreno L A, McGhee J G

机构信息

Endocrine Research Unit, San Francisco Veterans Administration Medical Center, California 94121.

出版信息

Endocrinology. 1988 Jul;123(1):382-9. doi: 10.1210/endo-123-1-382.

DOI:10.1210/endo-123-1-382

PMID:3260174

Abstract

Calcium and other divalent cations rapidly increase intracellular free Ca2+ ([Ca2+]i) in bovine parathyroid cells and inhibit PTH release. In other secretory cells, agonist-dependent generation of inositol trisphosphate (InsP3) through polyphosphoinositide turnover initiates the rise in [Ca2+]i by mobilizing Ca2+ from intracellular stores. To determine whether polyphosphoinositide breakdown is involved in mediating the response to Ca2+ and the divalent cations Ba2+, Mn2+, and Sr2+, we measured the production of inositol polyphosphates in parathyroid cells. Within 120 sec of increasing extracellular Ca2+ to 2.0 mM, InsP3, inositol bisphosphate (InsP2), and inositol monophosphate (InsP1) rose 95 +/- 37%, 87 +/- 17%, and 96 +/- 29%, respectively, vs. values in cells at 0.5 mM Ca2+ (n = 5). Raising extracellular Ca2+ from 0.5-3.0 mM produced even greater peak increments of 134 +/- 13%, 179 +/- 35%, and 313 +/- 65% in InsP3, InsP2, and InsP1, respectively, by 120 sec (n = 4). Similarly, within 10 sec of their addition, BaCl2 (2 mM), MnCl2 (2 mM), and SrCl2 (4 mM) stimulated the production of InsP3 56 +/- 2%, 152 +/- 31%, and 160 +/- 25%, respectively, vs. that in untreated cells at 0.5 mM Ca2+. At later time points, InsP2 and InsP1 were increased. The Ca2+ ionophore ionomycin at concentrations up to 500 nM had no effect on inositol phosphates, although it inhibited PTH release in a dose-dependent manner. Since high Ca2+ and other divalent cations depolarize parathyroid cells, we assessed the effect of high extracellular K+ on inositol polyphosphates. The addition of depolarizing concentrations of K+ (40 mM) did not change inositol phosphates. Thus, Ca2+ and other divalent cations increase the production of InsP3, InsP2, and InsP1 in parathyroid cells by a mechanism independent of increases in [Ca2+]i and of membrane depolarization. We conclude that parathyroid cells express membrane receptors or sensors for Ca2+ and other divalent cations linked to polyphosphoinositide turnover.

摘要

钙和其他二价阳离子可迅速增加牛甲状旁腺细胞内的游离钙离子浓度（[Ca2+]i），并抑制甲状旁腺激素（PTH）的释放。在其他分泌细胞中，通过多磷酸肌醇代谢产生的激动剂依赖性肌醇三磷酸（InsP3），通过从细胞内储存库中动员Ca2+来引发[Ca2+]i的升高。为了确定多磷酸肌醇分解是否参与介导对Ca2+以及二价阳离子Ba2+、Mn2+和Sr2+的反应，我们测量了甲状旁腺细胞中肌醇多磷酸的产生。将细胞外Ca2+浓度增加到2.0 mM后的120秒内，与0.5 mM Ca2+浓度下的细胞相比，InsP3、肌醇二磷酸（InsP2）和肌醇单磷酸（InsP1）分别升高了95±37%、87±17%和96±29%（n = 5）。将细胞外Ca2+浓度从0.5 mM提高到3.0 mM，在120秒时，InsP3、InsP2和InsP1的峰值增量分别更大，达到134±13%、179±35%和313±65%（n = 4）。同样，在添加BaCl2（2 mM）、MnCl2（2 mM）和SrCl2（4 mM）后的10秒内，与0.5 mM Ca2+浓度下未处理的细胞相比，它们分别刺激InsP3的产生增加了56±2%、152±31%和160±25%。在随后的时间点，InsP2和InsP1增加。浓度高达500 nM的Ca2+离子载体离子霉素对肌醇磷酸没有影响，尽管它以剂量依赖性方式抑制PTH释放。由于高Ca2+和其他二价阳离子可使甲状旁腺细胞去极化，我们评估了高细胞外K+对肌醇多磷酸的影响。添加去极化浓度的K+（40 mM）并没有改变肌醇磷酸。因此，Ca2+和其他二价阳离子通过一种独立于[Ca2+]i增加和膜去极化的机制，增加甲状旁腺细胞中InsP3、InsP2和InsP1的产生。我们得出结论，甲状旁腺细胞表达与多磷酸肌醇代谢相关的Ca2+和其他二价阳离子的膜受体或传感器。