Heparin specifically inhibits the inositol 1,4,5-trisphosphate-induced Ca2+ release from skinned rat aortic smooth muscle cells in primary culture

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Abstract
By measuring the 45Ca2+ movement in saponin-skinned primary cultured rat aortic smooth muscle cells, we examined the specificity of the inhibitory effect of heparin on the IP3-induced Ca2+ release. IP3 (100 μmol/l) markedly (98%) decreased the MgATP-dependent 45Ca2+ content in the non-mitochondrial Ca2+ stores in the presence of 1 μmol/l free Ca2+. Heparin (1–100 μg/ml) dose-dependently inhibited this Ca2+ release by IP3. In Ca2+-free solution, heparin (100 μg/ml) inhibited the increases in 45Ca2+ efflux rate evoked by 10 μmol/l IP3. De-N-sulfated heparin did not inhibit the IP3-induced Ca2+ release. Hyaluronic acid, heparan sulfate, chondroitin sulfate A, chondroitin sulfate B, chondroitin sulfate C and 2,6-disulfated d-glucosamine had no inhibitory effects on the IP3-induced Ca2+ release. High concentrations (over 1 mg/ml) of heparin inhibited the 45Ca2+ influx and decreased the Ca2+ content in skinned cells. These results suggest that heparin (1–100 μg/ml) specifically inhibits the IP3-induced increase in Ca2+ permeability of Ca2+ stores and that three sulfate groups at different locations on the molecule of heparin, two at the d-glucosamine and one at the iduronic acid, may be important for this action, in skinned vascular smooth muscle cells, in culture.