Seewald M J, Schlager J J, Olsen R A, Melder D C, Powis G
Department of Pharmacology, Mayo Clinic and Foundation, Rochester, MN 55905.
Cancer Commun. 1989;1(3):151-6.
High molecular weight (500 kDa) dextran sulfate (DXS) inhibited the release of Ca2+ induced by myoinositol 1,4,5-trisphosphate from non-mitochondrial stores of saponin-permeabilized Swiss 3T3 fibroblasts with an IC50 of 20 micrograms/mL. Low molecular weight (5 kDa) DXS did not have this effect. DXS was more inhibitory than heparin, which in the same system had an IC50 of 62 micrograms/mL. DXS also produced a small inhibition of Ca2+ release by arachidonic acid and GTP but did not affect Ca2+ release by 4-bromo A23187 or halothane. The transient increase in intracellular free Ca2+ concentration ([Ca2+]i) in intact Swiss 3T3 cells caused by platelet-derived growth factor was completely inhibited by 100 micrograms/mL of DXS, but DXS had no effect on the [Ca2+]i increase caused by bradykinin or vasopressin. The specific binding of platelet-derived growth factor, but not of bradykinin or vasopressin, to Swiss 3T3 fibroblasts was decreased by DXS. The effect of DXS in decreasing growth-factor mediated increases in [Ca2+]i may be mediated by an effect on the binding of growth factor to its receptor. An effect of DXS on the intracellular release of Ca2+ by second messengers to decrease changes in [Ca2+]i, however, cannot be ruled out.
高分子量（500 kDa）的硫酸葡聚糖（DXS）抑制了由肌醇1,4,5 - 三磷酸诱导的皂素通透的瑞士3T3成纤维细胞非线粒体钙库中钙离子的释放，其IC50为20微克/毫升。低分子量（5 kDa）的DXS没有这种作用。DXS比肝素更具抑制作用，在相同系统中肝素的IC50为62微克/毫升。DXS对花生四烯酸和GTP诱导的钙离子释放也有轻微抑制作用，但不影响4 - 溴A23187或氟烷诱导的钙离子释放。血小板衍生生长因子引起的完整瑞士3T3细胞内游离钙离子浓度（[Ca2+]i）的短暂升高被100微克/毫升的DXS完全抑制，但DXS对缓激肽或血管加压素引起的[Ca2+]i升高没有影响。DXS降低了血小板衍生生长因子与瑞士3T3成纤维细胞的特异性结合，但不影响缓激肽或血管加压素的结合。DXS降低生长因子介导的[Ca2+]i升高的作用可能是通过影响生长因子与其受体的结合来介导的。然而，不能排除DXS对第二信使介导的细胞内钙离子释放的影响，从而降低[Ca2+]i的变化。
