Suramin blocks intracellular Ca 2+ release and growth factor-induced increases in cytoplasmic free Ca 2+ concentration

Abstract

Suramin, a polysulfonated naphthylurea with antitumor activity, has been shown to be an inhibitor of the release of Ca 2+ 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 IC 50 for the effect of suramin was about 40 μM in both cases. Suramin did not block Ca 2+ release induced by the Ca 2+ ionophore 4-bromo A23187 or by the membrane perturbing agent halothane. Suramin, 7 × 10 −5 M, caused a 49% decrease in the elevation of intracellular free Ca 2+ concentration ([Ca 2+] i) caused by platelet derived growth factor (PDGF) in intact Swiss 3T3 fibroblasts but did not block the increases in [Ca 2+] 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 [Ca 2+] i response to growth factors may be mediated by a block of growth factor-receptor binding, but an effect on intracellular Ca 2+ release cannot be ruled out.