Calcium-independent phosphoinositide breakdown in rat basophilic leukemia cells. Evidence for an early rise in inositol 1,4,5-trisphosphate which precedes the rise in other inositol phosphates and in cytoplasmic calcium.
Calcium-independent phosphoinositide breakdown in rat basophilic leukemia cells. Evidence for an early rise in inositol 1,4,5-trisphosphate which precedes the rise in other inositol phosphates and in cytoplasmic calcium.
复制标题
大鼠嗜碱性白血病细胞中钙非依赖性磷酸肌醇分解。
DOI：
10.1016/s0021-9258(18)60827-0
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
H. Metzger
中科院分区：
文献类型：
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作者：
V. Pribluda;H. Metzger
在大鼠嗜碱性白血病细胞中，对免疫球蛋白 E (IgE) 具有高亲和力的受体聚集，导致磷酸肌醇发生钙依赖性和钙非依赖性水解。在没有钙的情况下诱导的磷酸肌醇水平的增加仅为 1 mM Ca2+ 观察到的增加的 25%。在 EGTA 刺激后 2 分钟，肌醇磷酸盐达到新的稳态水平，而在钙刺激下，它们会持续增加直至 15 分钟。当受体由于结合的 IgE 与抗原或抗 IgE 的相互作用，或通过化学交联的 IgE 的结合而聚集时，观察到类似的反应。抗原介导的反应被半抗原抑制，并且在刺激后后期这种抗原-抗体聚集体的破坏导致肌醇磷酸盐水平快速下降至基础值。通过 Dowex 柱对肌醇磷酸酯的分离表明，肌醇三磷酸酯快速上升，在 15 秒时达到峰值，并在 2 分钟内缓慢下降至较低平台。高压液相色谱分析显示，刺激后不到 10 秒，肌醇 1,4,5-三磷酸的水平增加了 5 倍，这先于其他肌醇磷酸的任何重大变化。在没有外部钙的情况下，受体的聚集会诱导细胞质钙的短暂增加，在激活后，细胞质钙的最大值最高可达基础水平约 25 nM。 Ca2+ 的上升开始滞后于肌醇 1,4,5-三磷酸的初始上升。
Aggregation of the receptor with high affinity for immunoglobulin E (IgE) in rat basophilic leukemia cells leads to a calcium-dependent and a calcium-independent hydrolysis of phosphoinositides. The increase in the levels of inositol phosphates induced in the absence of calcium is only 25% of that observed with 1 mM Ca2+. The inositol phosphates reach a new steady state level 2 min after stimulation in EGTA, whereas with calcium they continue to increase up to 15 min. A similar response is observed when the receptors are aggregated due to the interaction of bound IgE with antigen or with anit-IgE, or by the binding of IgE cross-linked chemically. The antigen-mediated response is inhibited by hapten and disruption of such antigen-antibody aggregates late after stimulation leads to a rapid decline in the levels of the inositol phosphates to basal values. Separation of the inositol phosphates by Dowex columns shows that there is a fast rise in inositol trisphosphate which peaks at 15 s and slowly declines to a lower plateau within 2 min. Analysis by high pressure liquid chromatography reveals a 5-fold increase in the levels of inositol 1,4,5-trisphosphate in less than 10 s after stimulation, which precedes any major change in the other inositol phosphates. Aggregation of the receptor in the absence of external calcium induces a transient increase in cytoplasmic calcium which reaches a maximum of approximately 25 nM over basal levels after activation. The onset of the rise in Ca2+ lags after the initial rise in the inositol 1,4,5-trisphosphate.