High molecular weight dextran sulfate inhibits intracellular Ca2+ release and decreases growth factor-induced increases in intracellular free Ca2+ in Swiss 3T3 fibroblasts.
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.
Seewald
M J
MJ
Department of Pharmacology, Mayo Clinic and Foundation, Rochester, MN 55905.
Schlager
J J
JJ
Olsen
R A
RA
Melder
D C
DC
Powis
G
G
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000378:metabolism; D001920:Bradykinin / Q000378:metabolism; D000001:Calcimycin / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D008934:Mitogens / Q000494:pharmacology; D008970:Molecular Weight; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism*
D001095:Arachidonic Acids; D003911:Dextrans; D008934:Mitogens; D010972:Platelet Activating Factor; D011956:Receptors, Cell Surface; D001127:Arginine Vasopressin; D016718:Arachidonic Acid; D000001:Calcimycin; C033170:4-bromo-A-23187; D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D006493:Heparin; D016264:Dextran Sulfate; D001920:Bradykinin; D002118:Calcium; D006221:Halothane