Heparin inhibits inositol trisphosphate-induced calcium release from permeabilized rat liver cells.

Neoplastic rat liver epithelial (261B) cells made permeable by electroporation released 0.2-0.3 microM Ca2+ from intracellular stores in response to 0.5 microM Ins(1,4,5)P3 stimulation. This Ca2+ release response was found to be inhibited by heparin in a dose-dependent manner (Ki of 15 micrograms/ml). Two other glycosaminoglycans, chondroitin sulfate and hyaluronic acid, showed no inhibitory effect at doses as high as 0.2 mg/ml. Passive Ca2+ release, and sequestration of Ca2+ into intracellular storage sites by the action of Ca2+-ATPase were unaffected by heparin treatment. We conclude that the inhibitory action of heparin treatment on Ca2+ mobilization in permeabilized 261B cells is mediated through its interaction at the Ins(1,4,5)P3 receptor binding site.