Suramin blocks intracellular Ca2+ release and growth factor-induced increases in cytoplasmic free Ca2+ concentration.
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.
Seewald
M J
MJ
Mayo Clinic Foundation, Department of Pharmacology, Rochester, MN 55905.
Olsen
R A
RA
Powis
G
G
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D013498:Suramin / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D014667:Vasopressins; D013498:Suramin; D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D001920:Bradykinin; D002118:Calcium