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

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

› Author Affiliations

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

References
1 Ross R, Glomset J, Kariya B, Harker L. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci USA 1974; 71: 1207-1210
2 Ross R, Glomset J. The pathogenesis of atherosclerosis. N Engl J Med 1976; 295: 368-377
3 Weksler BB, Nachman RL. Platelets and atherosclerosis. A J Med 1981; 71: 331-333
4 Mustard JD, Packham MA. The role of blood and platelets in atherosclerosis and the complication of atherosclerosis. Thromb Diath Haemorrh 1975; 33: 444-456
5 Carvalho AC A, Colman RW, Lees RS. Platelet function in hyperlipoproteinemia. N Engl J Med 1974; 290: 434-438
6 Tremoli E, Maderna P, Sirtori M, Sirtori CR. Platelet aggregation and malondialdehyde formation in type Ila hypercholesterolemic patients. Elaemostasis 1979; 8: 47-53
7 Shattil SJ, Anaya-Galindo R, Bennett J, Colman RW, Cooper RA. Platelet hypersensitivity induced by cholesterol incorporation. J Clin Invest 1975; 55: 636-643
8 Stuart MJ, Gerrard JM, White JG. Effect of cholesterol on production of thromboxane B2 by platelets in vitro. N Engl J Med 1980; 302: 6-10
9 Kramer RM, Jakubowski JA, Vaillancourt R, Deykin D. Effect of membrane cholesterol on phospholipid metabolism in thrombin-stimulated platelets. J Biol Chem 1982; 257: 6844-6849
10 Tandon N, Harmon JT, Rodbard D, Jamieson GA. Thrombin receptors define responsiveness of cholesterol-modified platelets. J Biol Chem 1983; 258: 11840-11845
11 Shattil SJ, Bennett JS, Colman RW, Cooper RA. rAbnormalities of cholesterol-phospholipid composition in platelets and low-density lipoproteins of human hyperbetalipoproteinemia. J Lab Clin Med 1977; 89: 341-353
12 Insel PA, Nirenberg P, Turnbull J, Shattil SJ. Relationship between membrane cholesterol, a-adrenergic receptors, and platelet function. J Am Chem Soc 1978; 17: 5269-5274
13 Hamberg M, Svensson J, Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci USA 1975; 72: 2994-2998
14 Kaibuchi K, Tsuda T, Kikuchi A, Tanimoto T, Takai Y. Enhancement of collagen-induced phosphoinositide turnover by thromboxane A2 analogue through Ca2+ mobilization in human platelets. FEBS Lett 1985; 192: 104-108
15 Tremoli E, Maderna P, Colli S, Morazzoni G, Sirtori CR. Increased platelet sensitivity and thromboxane B2 formation in type Ila hyper-lipoproteinemic patients. Eur J Clin Invest 1984; 14: 329-333
16 Moriyama T, Takamura H, Narita H, Tanaka K, Matsuura T, Kito M. Elevation of cytosolic free Ca2+ is directly evoked by thromboxane A2 in human platelets during activation with collagen. J Biochem 1988; 103: 901-902
17 Ushikubi F, Okuma M, Kanaji K, Sugiyama T, Ogorochi T, Narumiya S, Uchino H. Hemorrhagic thrombocytopathy with platelet thromboxane A2 receptor abnormality; defective signal transduction with normal binding activity. Thromb Haemostas 1987; 57: 158-164
18 Yamamoto K, Hirai A, Tamura Y, Yoshida S. A combined method for the preparation of washed human platelets using prostacyclin and gel filtration. Thromb Res 1988; 50: 733-738
19 Takenaga M, Kitagawa H, Hirai A, Tamura Y, Yoshida S. Mechanism of anti-platelet aggregatory action of dilazep. J Pharmacobio-Dyn 1985; 8: 77-83
20 Takenaga M, Hirai A, Terano T, Tamura Y, Kitagawa H, Yoshida S. Comparison of the in vitro effect of eicosapentaenoic acid (EPA)-derived lipoxygenase metabolites on human platelet function with those of arachidonic acid. Thromb Res 1986; 37: 373-384
21 Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 1985; 260: 3440-3450
22 Yagihara Y, Bleasdale JE, Hawthorne JN. Effects of acetylcholine on the incorporation of [32P]orthophosphate in vitro into the phospholipids of subsynaptosomal membranes from guinea-pig brain. J Neuro Chem 1973; 21: 173-190
23 Shaikh NA, Palmer FB St C. Phosphoinositide kinases in chick brain and sciatic nerve, a developmental study. J Neurochem 1977; 28: 395-402
24 Narumiya S, Okuma M, Ushikubi F. Binding of a radioiodinated 13-azapinane thromboxane antagonist to platelets: correlation with antiaggregatory activity in different species. Br J Pharmacol 1986; 88: 323-331
25 Hassall DG, Forrest LA, Bruckdorfer KR, Marenah CB, Turner P, Cortese C, Miller NE, Lewis B. Influence of plasma lipoproteins on platelet aggregation in a normal male population. Arteriosclerosis 1983; 3: 332-338
26 Chen PS, Toribara TY, Warner H. Microdetermination of phosphorus. Anal Chem 1956; 28: 1756-1758
27 Tallarida RJ, Murray RB. Manual of Pharmacologic Calculations with Computer Programs. (2nd ed.) Springer-Verlag, New York 1986
28 Morinelli TA, Niewiarowski S, Daniel JL, Smith JB. Receptor-mediated effects of a PGH₂ analogue (U46619) on human platelets. Am J Physiol 1987; 253: H1035-H1043
29 Koutouzov S, Remmal A, Marche P, Meyer P. Hypersensitivity of phospholipase C in platelets of spontaneously hypertensive rats. Hypertension 1987; 10: 497-504
30 Halushka PV, Kochel PJ, Mais DE. Binding of thromboxane A₂/ prostaglandin H₂ agonists to human platelets. Br J Pharmacol 1987; 91: 223-227
31 Mais DE, Burch RM, Saussy JrD L, Kochel PJ, Halushka PV. Binding of a thromboxane A2/prostaglandin H2 receptor antagonist to washed human platelets. J Pharmacol Exp Ther 1985; 235: 729-734
32 Ogletree ML, Harris DN, Greenberg R, Haslanger MF, Nakane M. Pharmacological actions of SQ29548, a novel selective thromboxane antagonist. J Pharmacol Exp Ther 1985; 234: 435-441
33 Liel N, Mais DE, Halushka PV. Binding of a thromboxane A2/ prostaglandin H2 agonist [3H]U46619 to washed platelets. Prostaglandins 1987; 33: 789-795
34 Yamamoto K, Hirai A, Tamura Y, Yoshida S. In vitro and in vivo effect of ginseng saponins, major components of Korean red ginseng on human platelet aggregation and arachidonic acid metabolism. J Med Pharm Soc WAKAN-YAKU 1988; 5: 184-190
35 Sato T, Maegawa H, Kometani M, Fujii T. Collagen-induced calcium influx is enhanced in platelets from hypercholesterolemic rabbits. Thromb Res 1985; 40: 59-68