Hypersensitivity to Thromboxane A2 in Cholesterol-Rich Human Platelets

Takuya Tomizuka; Kyohei Yamamoto; Aizan Hirai; Yasushi Tamura; Sho Yoshida

doi:10.1055/s-0038-1647364

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1990; 64(04): 594-599
DOI: 10.1055/s-0038-1647364

Original Article

Schattauer GmbH Stuttgart

Hypersensitivity to Thromboxane A₂ in Cholesterol-Rich Human Platelets

Authors

Takuya Tomizuka

The 2nd Department of Internal Medicine, School of Medicine, Chiba University, Chiba, Japan
Kyohei Yamamoto

The 2nd Department of Internal Medicine, School of Medicine, Chiba University, Chiba, Japan
Aizan Hirai

The 2nd Department of Internal Medicine, School of Medicine, Chiba University, Chiba, Japan
Yasushi Tamura

The 2nd Department of Internal Medicine, School of Medicine, Chiba University, Chiba, Japan
Sho Yoshida

The 2nd Department of Internal Medicine, School of Medicine, Chiba University, Chiba, Japan

Abstract

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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.

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References

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