Hypersensitivity to thromboxane A2 in cholesterol-rich human platelets.
The effect of changes in platelet membrane cholesterol content on thromboxane A2 (TXA2)-induced platelet activation was studied. Concentrations of 9,11-epithio-11,12-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 (Bmax) for SQ29548 was significantly increased in cholesterol-rich platelets compared with cholesterol-normal platelets, while the equilibrium dissociation rate constant (Kd) 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.
Tomizuka
T
T
2nd Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Yamamoto
K
K
Hirai
A
A
Tamura
Y
Y
Yoshida
S
S
D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D002250:Carbon Radioisotopes; D002784:Cholesterol / Q000097:blood*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008055:Lipids / Q000097:blood; D008081:Liposomes; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010761:Phosphorus Radioisotopes; D010974:Platelet Aggregation / Q000187:drug effects; D011982:Receptors, Prostaglandin / Q000097:blood; D017482:Receptors, Thromboxane; D012701:Serotonin / Q000097:blood; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D008055:Lipids; D008081:Liposomes; D010712:Phosphatidic Acids; D010761:Phosphorus Radioisotopes; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D012701:Serotonin; D013928:Thromboxane A2; C037866:STA 2; D002784:Cholesterol; D002118:Calcium