Strontium Ions Stimulate The Metabolism Of Phosphoinositides In Human Blood Platelets

We have previously shown that strontium ions (Sr2+ ) cause platelet 5-hydroxytryptamine secretion and thromboxane (TxB2) production in parallel. Here, we have further investigated the mechanism by which Sr2+ causes platelet TXB2 production and platelet activation by examining phospholipid metallism in washed human platelets in response to Sr2+ . Platelet phospholipid pools were labelled by preincubation with 3H- glycerol. Phospholipids and neutral lipids were extracted with chloroform-methanol and resolved bytwo-dimensional thin layer chromatography. Sr2+ (l-8mM) produced a marked depletion in platelet phosphatidyl inositol (PI) with a maximal effect at 10 minutes. The major products corresponded to polyphosphoinositides (PPIs) and lysophosphatidyl inositol (LPI). No significant changes in other phospholipids were detected. Similarly, no consistent effects were observed on mono or diglyceride levels. PI breakdown in response to Sr2+ was inhibited by Ca , prostaglandin E1, and trifluoperazine, suggesting the possible involvement of calmodulin in Sr2+ action. PI break-down was also partially inhibited by aspirin and indomethacin but not by imidazole. We suggest that Sr2+ induces platelet secretion and TXB2 production by causing the specific break down of PI, presumably by activating a phospholipase. The significance of the observed effect upon PPI metabolism is unknown, although PPI turnover may be closely associated with the control of calcium fluxes. Thus, Sr2+ may mimick a rise in cytosol Ca2+ in the platelet which is thought to accompany platelet activation.