In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

Margaret L Rand; Peter L Gross; Donna M Jakowec; Marian A Packham; J Fraser Mustard

doi:10.1055/s-0038-1646570

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1989; 61(02): 254-258
DOI: 10.1055/s-0038-1646570

Original Article

Schattauer GmbH Stuttgart

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

Authors

Margaret L Rand

The Department of Biochemistry, University of Toronto, Toronto, Ont., Canada, and the Department of Pathology, McMaster University, Hamilton, Ont., Canada
Peter L Gross

The Department of Biochemistry, University of Toronto, Toronto, Ont., Canada, and the Department of Pathology, McMaster University, Hamilton, Ont., Canada
Donna M Jakowec

The Department of Biochemistry, University of Toronto, Toronto, Ont., Canada, and the Department of Pathology, McMaster University, Hamilton, Ont., Canada
Marian A Packham

The Department of Biochemistry, University of Toronto, Toronto, Ont., Canada, and the Department of Pathology, McMaster University, Hamilton, Ont., Canada
J Fraser Mustard

The Department of Biochemistry, University of Toronto, Toronto, Ont., Canada, and the Department of Pathology, McMaster University, Hamilton, Ont., Canada

Abstract

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Summary

Ethanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI₂), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI₂ were very similar to its inhibitory effects in the absence of PGI₂, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI₂ did not appear to be brought about by further increases in platelet cyclic AMP levels.

Keywords

Platelet responses - Ethanol - Prostacyclin - Cyclic AMP

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References

References
1 Klatsky AL, Friedman GD, Siegelaub AB. Alcohol and mortality. A ten-year Kaiser-Permanente experience Ann Intern Med 1981; 95: 139-145
2 Marmot MG, Rose G, Shipley MJ, Thomas BJ. Alcohol and mortality: A U-shaped curve. Lancet 1981; 1: 580-583
3 Gordon T, Kannel WB. Drinking and mortality. The Framingham study Am J Epidemiol 1984; 120: 97-107
4 Moore RD, Pearson TA. Moderate alcohol consumption and coronary artery disease. A review Medicine 1986; 65: 242-266
5 Friedman LA, Kimball AW. Coronary heart disease mortality and alcohol consumption in Framingham. Am J Epidemiol 1986; 124: 481-489
6 Davis JW, Phillips PE. The effect of ethanol on human platelet aggregation in vitro. Atherosclerosis 1970; 11: 473-477
7 Haut MJ, Cowan DH. The effect of ethanol on hemostatic properties of human blood platelets. Am J Med 1974; 56: 22-33
8 McGregor L, Renaud S. Inhibitory effect of alcohol on platelet functions of rats fed saturated fats. Thromb Res 1981; 22: 221-225
9 Fenn CG, Littleton JM. Inhibition of platelet aggregation by ethanol in vitro shows specificity for aggregating agent used and is influenced by platelet lipid composition. Thromb Haemostas 1982; 48: 49-53
10 Rand ML, Packham MA, Kinlough-Rathbone RL, Mustard JF. Effects of ethanol on pathways of platelet aggregation in vitro. Thromb Haemostas 1988; 59: 383-387
11 Stuart MJ. Ethanol-inhibited platelet prostaglandin synthesis in vitro. J Stud Alcohol 1979; 40: 1-6
12 Hwang DH. Ethanol inhibits the formation of endoperoxide metabolites in human platelets. Prostaglandins Med 1981; 7: 511-513
13 Hwang DH, LeBlanc P, Chanmugan P. In vitro and in vivo effects of ethanol on the formation of endoperoxide metabolites in rat platelets. Lipids 1981; 16: 583-588
14 Fenn GC, Lynch MA, Nhamburo PT, Caberos L, Littleton JM. Comparison of effects of ethanol on platelet function and synaptic transmission. Pharmacol Biochem Behav 1983; 18 Suppl (Suppl. 01) 37-43
15 Rand ML, Vickers JD, Kinlough-Rathbone RL, Packham MA, Mustard JF. Thrombin-induced inositol trisphosphate production by rabbit platelets is inhibited by ethanol. Biochem J 1988; 251: 279-284
16 Landolfi R, Steiner M. Ethanol raises prostacyclin in vivo and in vitro. Blood 1984; 64: 679-682
17 Karanian JW, Stojanov M, Salem Jr N. Effect of ethanol on prostacyclin and thromboxane A₂synthesis in rat aortic rings in vitro. Prostaglandins Leukotrienes Med 1985; 20: 175-186
18 Mehta P, Mehta J, Lawson D, Patel S. Ethanol stimulates prostacyclin biosynthesis by human neutrophils and potentiates anti-platelet aggregatory effects of prostacyclin. Thromb Res 1987; 48: 653-661
19 Weksler BB. Prostacyclin. In: Progress in Hemostasis and Thrombosis Vol. 6. Spaet TH. (ed) Grove and Stratton; New York: 1982. pp 113-138
20 Jakubowski JA, Vaillancourt R, Deykin D. Interation of ethanol, prostacyclin, and aspirin in determining human platelet reactivity in vitro. Arteriosclerosis 1988; 8: 436-441
21 Cazenave J-P, Packham MA, Mustard JF. Adherence of platelets to a collagen-coated surface: development of a quantitative method. J Lab Clin Med 1973; 82: 978-990
22 Davies JA, Essien E, Cazenave J-P, Kinlough-Rathbone RL, Gent M, Mustard JF. The influence of red blood cells on the effects of aspirin or sulphinpyrazone on platelet adherence to damaged rabbit aorta. Br J Haematol 1979; 42: 283-291
23 Kinlough-Rathbone RL, Packham MA, Mustard JF. Platelet aggregation. In: Methods in Hematology. Measurements of Platelet Function. Harker LA, Zimmerman TS. (eds) Churchill Livingstone; Edinburgh: 1983. pp 64-91
24 Molnar J, Lorand L. Studies on apyrases. Arch Biochem Biophys 1961; 93: 353-363
25 Ardlie NG, Packham MA, Mustard JF. Adenosine diphosphate- induced platelet aggregation in suspensions of washed rabbit platelets. Br J Haematol 1970; 19: 7-17
26 Ardlie NG, Perry DW, Packham MA, Mustard JF. Influence of apyrase on stability of suspensions of washed rabbit platelets. Proc Soc Exp Biol Med 1971; 136: 1021-1023
27 Greenberg J, Packham MA, Cazenave J-P, Reimers H-J, Mustard JF. Effects on platelet function of removal of platelet sialic acid by neuraminidase. Lab Invest 1975; 32: 476-484
28 Haslam RJ, McClenaghan MD. Measurement of circulating prostacyclin. Nature 1981; 292: 364-366
29 Packham MA, Kinlough-Rathbone RL, Mustard JF. Thromboxane A₂causes feedback amplification involving extensive thromboxane A₂formation upon close contact of human platelets in media with a low concentration of ionized calcium. Blood 1987; 70: 647-651
30 Stubbs CD, Smith AD. The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochim Biophys Acta 1984; 779: 89-137
31 Chin JH, Goldstein DB. Effects of low concentrations of ethanol on the fluidity of spin-labeled erythrocyte and brain membranes. Mol Pharmacol 1977; 13: 435-441
32 Gordon AS, Collier K, Diamond I. Ethanol regulation of adenosine receptor-stimulated cAMP levels in a clonal neural cell line: An in vitro model of cellular tolerance to ethanol. Proc Natl Acad Sci USA 1986; 83: 2105-2109
33 Rotrosen J, Mandio D, Segamick D, Traficante LJ, Gershon S. Ethanol and prostaglandin E₁: Biochemical and behavioural interactions. Life Sci 1980; 26: 167-176
34 Packham MA, Mustard JF. Normal and abnormal platelet activity. In: Blood Platelet Function and Medicinal Chemistry. Lasslo A. (ed) Elsevier; New York: 1984. pp 61-128
35 Meyers KM. Species differences. In: Platelet Responses and Metabolism. Vol. 1. Responses. Holmsen H. (ed) CRC Press; Boca Raton: 1986. pp 209-234
36 Lages B, Weiss HJ. Dependence of human platelet functional responses on divalent cations: Aggregation and secretion in heparin- and hirudin-anticoagulated platelet-rich plasma and the effects of chelating agents. Thromb Haemostas 1981; 45: 173-179
37 Kinlough-Rathbone RL, Cazenave J-P, Packham MA, Mustard JF. Effect of inhibitors on the arachidonate pathway on the release of granule contents from rabbit platelets adherent to collagen. Lab Invest 1979; 42: 28-34