Hypersensitivity to Thromboxane A₂ in Cholesterol-Rich Human Platelets

Summary

The effect of changes in platelet membrane cholesterol content on thromboxane A₂ (TXA₂)-induced platelet activation was studied. Concentrations of 9,ll-epithio-ll,12-methano-TXA₂ (STA₂), a stable analogue of TXA₂ which can cause half-maximal aggregation and release of [¹⁴C]serotonin in cholesterol-rich platelets were significantly lower than those in cholesterol-normal platelets. STA₂-induced increase in cytosolic calcium concentration and [³²P]phosphatidic acid formation in cholesterol-rich platelets were significantly greater than those in cholesterol-normal platelets. The maximal concentration of binding site (B_max) for SQ29548 was significantly increased in cholesterol-rich platelets compared with cholesterol-normal platelets, while the equilibrium dissociation rate constant (K_d) for SQ29548 did not differ between cholesterol-rich and cholesterol-normal platelets. The present study suggested that sensitivity to TXA₂ was increased by the incorporation of cholesterol into platelet membrane and that the cause of hypersensitivity to TXA₂ in cholesterol-rich platelets may be partly explained by an increase in binding capacity for TXA₂.

• References

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