Taylor C W, Potter B V
Department of Pharmacology, University of Cambridge, U.K.
Biochem J. 1990 Feb 15;266(1):189-94. doi: 10.1042/bj2660189.
An explanation of the complex effects of hormones on intracellular Ca2+ requires that the intracellular actions of Ins(1,4,5)P3 and the relationships between intracellular Ca2+ stores are fully understood. We have examined the kinetics of 45Ca2+ efflux from pre-loaded intracellular stores after stimulation with Ins(1,4,5)P3 or the stable phosphorothioate analogue, Ins(1,4,5)P3[S]3, by simultaneous addition of one of them with glucose/hexokinase to rapidly deplete the medium of ATP. Under these conditions, a maximal concentration of either Ins(1,4,5)P3 or Ins(1,4,5)P3[S]3 evoked rapid efflux of about half of the accumulated 45Ca2+, and thereafter the efflux was the same as occurred under control conditions. Submaximal concentrations of Ins(1,4,5)P3 or Ins(1,4,5)P3[S]3 caused a smaller rapid initial efflux of 45Ca2+, after which the efflux was similar whatever the concentration of Ins(1,4,5)P3 or Ins(1,4,5)P3[S]3 present. The failure of submaximal concentrations of Ins(1,4,5)P3 and Ins(1,4,5)P3[S]3 to mobilize fully the Ins(1,4,5)P3-sensitive Ca2+ stores despite prolonged incubation was not due either to inactivation of Ins(1,4,5)P3 or to desensitization of the Ins(1,4,5)P3 receptor. The results suggest that the size of the Ins(1,4,5)P3 sensitive Ca2+ stores depends upon the concentration of Ins(1,4,5)P3.
要解释激素对细胞内钙离子的复杂作用，就需要充分了解肌醇-1,4,5-三磷酸（Ins(1,4,5)P3）的细胞内作用以及细胞内钙库之间的关系。我们通过将Ins(1,4,5)P3或其稳定的硫代磷酸类似物Ins(1,4,5)P3[S]3之一与葡萄糖/己糖激酶同时添加，以快速耗尽培养基中的三磷酸腺苷（ATP），从而研究了用Ins(1,4,5)P3刺激后预加载的细胞内钙库中45Ca2+的流出动力学。在这些条件下，Ins(1,4,5)P3或Ins(1,4,5)P3[S]3的最大浓度会引起约一半累积的45Ca2+快速流出，此后流出情况与对照条件下相同。Ins(1,4,5)P3或Ins(1,4,5)P3[S]3的亚最大浓度引起45Ca2+较小的快速初始流出，之后无论存在的Ins(1,4,5)P3或Ins(1,4,5)P3[S]3浓度如何，流出情况都相似。尽管长时间孵育，但Ins(1,4,5)P3和Ins(1,4,5)P3[S]3的亚最大浓度未能完全动员Ins(1,4,5)P3敏感的钙库，这既不是由于Ins(1,4,5)P3失活，也不是由于Ins(1,4,5)P3受体脱敏。结果表明，Ins(1,4,5)P3敏感钙库的大小取决于Ins(1,4,5)P3的浓度。
