Seewald M J, Olsen R A, Powis G
Mayo Clinic Foundation, Department of Pharmacology, Rochester, MN 55905.
Cancer Lett. 1990 Feb;49(2):107-13. doi: 10.1016/0304-3835(90)90145-n.
Suramin, a polysulfonated naphthylurea with antitumor activity, has been shown to be an inhibitor of the release of Ca2+ from non-mitochondrial stores induced by the putative intracellular second messengers inositol 1, 4, 5-trisphosphate and GTP in saponin permeabilized Swiss 3T3 fibroblasts. The IC50 for the effect of suramin was about 40 microM in both cases. Suramin did not block Ca2+ release induced by the Ca2+ ionophore 4-bromo A23187 or by the membrane perturbing agent halothane. Suramin, 7 x 10(-5) M, caused a 49% decrease in the elevation of intracellular free Ca2+ concentration ([Ca2+]i) caused by platelet derived growth factor (PDGF) in intact Swiss 3T3 fibroblasts but did not block the increases in [Ca2+]i caused by bradykinin or vasopressin. Suramin decreased PDGF binding to its receptor on intact Swiss 3T3 fibroblasts but had no effect on the binding of bradykinin and vasopressin. The results show that the effect of suramin in decreasing the [Ca2+]i response to growth factors may be mediated by a block of growth factor-receptor binding, but an effect on intracellular Ca2+ release cannot be ruled out.
苏拉明是一种具有抗肿瘤活性的多磺酸萘脲，已被证明是一种抑制剂，可抑制皂素通透的瑞士3T3成纤维细胞中由假定的细胞内第二信使肌醇1,4,5 - 三磷酸和GTP诱导的非线粒体钙库释放Ca2+。在这两种情况下，苏拉明作用的IC50约为40 microM。苏拉明不会阻断由Ca2+离子载体4 - 溴A23187或膜扰动剂氟烷诱导的Ca2+释放。7×10(-5) M的苏拉明使完整瑞士3T3成纤维细胞中由血小板衍生生长因子（PDGF）引起的细胞内游离钙浓度（[Ca2+]i）升高降低了49%，但不会阻断缓激肽或血管加压素引起的[Ca2+]i升高。苏拉明降低了完整瑞士3T3成纤维细胞上PDGF与其受体的结合，但对缓激肽和血管加压素的结合没有影响。结果表明，苏拉明降低对生长因子的[Ca2+]i反应的作用可能是通过阻断生长因子 - 受体结合介导的，但不能排除对细胞内Ca2+释放的影响。
