Abstract
We studied the effect of heparin on the inositol 1, 4, 5-triphosphate (IP3)-dependent increase in intracellular calcium (Ca2+) caused by ATP. The Ca2+ concentration ([Ca2+]i) in cultured epithelial cells from cow tracheas was measured by the fura-2 method. ATP (10-4M) stimulated IP3 production and caused a biphasic increase in [Ca2+]i: a transient response and a subsequent sustained response. Heparin (1-100U/ml) dose-dependently inhibited the ATP-induced increase in [Ca2+]i, but had no effect on IP3 production. Dextran sulfate, a polysaccharide with negative charge density, had a similar inhibitory effect on the ATP-induced increase in [Ca2+]i. These data suggest that heparin inhibits intracellular Ca2+ mobilization by acting at a site “distal to” IP3 production, and that the mechanism of action of heparin may be related to its negative charge.