O'Neill Allison F, Hagar Robert E, Zipfel Warren R, Nathanson Michael H, Ehrlich Barbara E
Department of Medicine, Yale University, New Haven, CT 06520, USA.
Biochem Biophys Res Commun. 2002 Jun 14;294(3):719-25. doi: 10.1016/S0006-291X(02)00524-7.
It has been proposed that the inositol 1,4,5-trisphosphate receptor (InsP(3)R) type III acts as a trigger for InsP(3)-mediated calcium (Ca(2+)) signaling, because this InsP(3) isoform lacks feedback inhibition by cytosolic Ca(2+). We tested this hypothesis in RIN-m5F cells, which express predominantly the type III receptor. Extracellular ATP increases Ca(2+) in these cells, and we found that this effect is independent of extracellular Ca(2+) but is blocked by the InsP(3)R antagonist heparin. There was a dose-dependent increase in the number of cells responding to ATP and two-photon flash photolysis of caged-Ca(2+) heightened the sensitivity of RIN-m5F cells to this increase. These findings provide evidence that Ca(2+) increases the sensitivity of the InsP(3)R type III in intact cells and supports the idea that this isoform can act as a trigger for hormone-induced Ca(2+) signaling.
有人提出，III型肌醇1,4,5-三磷酸受体（InsP(3)R）作为InsP(3)介导的钙（Ca(2+)）信号传导的触发因素，因为这种InsP(3)亚型缺乏胞质Ca(2+)的反馈抑制作用。我们在主要表达III型受体的RIN-m5F细胞中验证了这一假设。细胞外ATP可使这些细胞中的Ca(2+)增加，并且我们发现这种效应不依赖于细胞外Ca(2+)，但可被InsP(3)R拮抗剂肝素阻断。对ATP作出反应的细胞数量呈剂量依赖性增加，而笼锁Ca(2+)的双光子闪光光解增强了RIN-m5F细胞对这种增加的敏感性。这些发现提供了证据，表明Ca(2+)可增加完整细胞中III型InsP(3)R的敏感性，并支持了这种亚型可作为激素诱导的Ca(2+)信号传导触发因素的观点。
