Dextran sulfate inhibits the inositol 1,4,5-trisphosphate-induced Ca2+ release from skinned and cultured smooth muscle cells

Dextran sulfate inhibited the inositol 1,4,5-trisphosphate (IP3)-induced decrease in 45Ca2+ content, in a dose-dependent manner, in saponin-skinned and primary cultured smooth muscle cells from the rat aorta. The maximum inhibition was observed at 3-10 mg/ml, and the IC50 was about 173 micrograms/ml. Dextran sulfate also inhibited the IP3-induced increase in 45Ca2+ efflux rate, but did not affect the caffeine-induced Ca2+ release. Dextran sulfate inhibited the specific binding of [4,5-32P]IP3 to the skinned cells, thereby indicating that it may have an effect on the IP3 receptor. Dextran (without the sulfates) had no inhibitory effect on either the IP3-induced Ca2+ release or on the specific binding of [4,5-32P]IP3. Thus, sulfate groups on the molecule of dextran sulfate may play an important role in the inhibition of the IP3-induced Ca2+ release from intracellular stores.