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DOI: 10.1055/s-0038-1647500
Effects of Ethanol on Pathways of Platelet Aggregation In Vitro
Publication History
Received 24 August 1987
Accepted after revision 11 January 1988
Publication Date:
29 June 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/198803/lookinside/thumbnails/10-1055-s-0038-1647500-1.jpg)
Summary
Ethanol, at physiologically tolerable concentrations, did not affect the primary phase of ADP-induced aggregation of human or rabbit platelets, which is not associated with the secretion of granule contents. Potentiation by epinephrine of the primary phase of ADP-induced aggregation of rabbit platelets was also not inhibited by ethanol. However, ethanol did inhibit the secondary phase of ADP-induced aggregation which occurs with human platelets in citrated platelet-rich plasma and is dependent on the formation of thromboxane A2. Inhibition by ethanol of thromboxane production by stimulated platelets is likely due to inhibition of the mobilization of arachidonic acid from membrane phospholipids, as ethanol had little or no effect on aggregation and secretion induced by arachidonic acid or the thromboxane mimetic U46619. Rabbit platelet aggregation and secretion in response to low concentrations of collagen, thrombin, or PAF were inhibited by ethanol. Inhibition of the effects of thrombin and PAF was also observed with aspirin-treated platelets. Thus, in addition to inhibiting the mobilization of arachidonate for thromboxane formation that occurs with most agonists, ethanol can also inhibit aggregation and secretion through other effects on platelet responses.
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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 Hennekens CH, Willett W, Rosner B, Cole DS, Mayrent SL. Effects of beer, wine, and liquor in coronary deaths. JAMA 1979; 242: 1973-1974
- 7 Landolfi R, Steiner M. Ethanol raises prostacyclin in vivo and in vitro. Blood 1984; 64: 679-682
- 8 Davis JW, Phillips PE. The effect of ethanol on human platelet aggregation in vitro. Atherosclerosis 1970; 11: 473-477
- 9 Haut MJ, Cowan DH. The effect of ethanol on hemostatic properties of human blood platelets. Am J Med 1974; 56: 22-33
- 10 McGregor L, Renaud S. Inhibitory effect of alcohol on platelet functions of rats fed saturated fats. Thromb Res 1981; 22: 221-225
- 11 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
- 12 Stuart MJ. Ethanol-inhibited platelet prostaglandin synthesis in vitro. J Stud Alcohol 1979; 40: 01-06
- 13 Hwang DH. Ethanol inhibits the formation of endoperoxide metabolites in human platelets. Prostaglandins Med 1981; 7: 511-513
- 14 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
- 15 Packham MA, Mustard JF. The role of platelets in the development and complications of atherosclerosis. Semin Hematol 1986; 23: 08-26
- 16 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
- 17 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
- 18 Tandon N, Harmon JT, Rodbard D, Jamieson GA. Thrombin receptors define responsiveness of cholesterol-modified platelets. J Biol Chem 1983; 258: 11840-11845
- 19 MacIntyre DE, Hoover RL, Smith M, Steer M, Lynch C, Karnovsky MJ, Salzman EW. Inhibition of platelet function by cis-unsaturated fatty acids. Blood 1984; 63: 848-857
- 20 Packham MA, Mustard JF. Normal and abnormal platelet activity. In: Blood Platelet Function and Medicinal Chemistry. Lasslo A. Elsevier; New York: 1984. p 61-128
- 21 Holmsen H. Platelet secretion. In: Hemostasis and Thrombosis, Basic Principles and Clinical Practice. Colman RW, Hirsh J, Marder VJ, Salzman EW. Lippincott; Philadelphia: 1987: 606-617
- 22 Rand ML, Groves HM, Kinlough-Rathbone RL, Packham MA, Mustard JF. Effects of ethanol on rabbit platelet responses to collagen in vitro and ex vivo and on platelet adhesion to de-endothelialized aortae in vivo. Thromb Res 1987; 48: 379-388
- 23 Kinlough-Rathbone RL, Reimers HJ, Mustard JF, Packham MA. Sodium arachidonate can induce platelet shape change and aggregation which are independent of release reaction. Science 1976; 192: 1011-1102
- 24 Mustard JF, Perry DW, Kinlough-Rathbone RL, Packham MA. Factors responsible for ADP-induced release reaction of human platelets. Am J Physiol 1975; 228: 1757-1765
- 25 Lawrie JS, Ross J, Kemp GD. Purification of fibrinogen and the separation of its degradation products in the presence of calcium ions. Biochem Soc Trans 1979; 07: 693-694
- 26 Kinlough-Rathbone RL, Packham MA, Mustard JF. Platelet aggregation. In: Methods in Hematology. Measurements of Platelet Function. Harker LA, Zimmerman TS. Churchill-Livingston; Edinburgh: 1983. p 64-91
- 27 Molnar J, Lorand L. Studies on apyrases. Arch Biochem Biophys 1961; 93: 353-363
- 28 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
- 29 Ardlie NG, Packham MA, Mustard JF. Adenosine diphosphate-induced platelet aggregation in suspensions of washed rabbit platelets. Br J Haematol 1970; 19: 07-17
- 30 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
- 31 Kinlough-Rathbone RL, Packham MA, Mustard JF. Comparison of methods of measuring loss of cytoplasmic constituents from platelets. Thromb Res 1976; 9: 669-673
- 32 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
- 33 Packham MA, Kinlough-Rathbone RL, Mustard JF. Thromboxane A2 causes feedback amplification involving extensive thromboxane A2 formation upon close contact of human platelets in media with a low concentration of ionized calcium. Blood 1987; 70: 647-651
- 34 Meyers KM. Species differences. In: Platelet Responses and Metabolism. Vol. 1. Responses. Holmsen H. CRC Press; Boca Raton: 1986: 209-234
- 35 Hallam TJ, Scrutton MC. Responses of rabbit platelets to adrenaline induced by other agonists. Thromb Res 1981; 21: 413-424
- 36 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
- 37 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
- 38 Berridge MJ, Irvine RF. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 1984; 312: 315-321
- 39 Brass LF, Joseph SK. A role for inositol triphosphate in intracellular Ca2+ mobilization and granule secretion in platelets. J Biol Chem 1985; 260: 15172-15179
- 40 Chignard M, Lalau Keraly C, Nunez D, Coeffier E, Benveniste J. PAF-acether and platelets. In: Platelets in Biology and Pathology III. MacIntyre DE, Gordon JL. Elsevier; New York: 1987: 289-315
- 41 Shinitzky M. Membrane fluidity and cellular functions. In: Physiology of Membrane Fluidity. Vol. 1. Shinitzky M. CRC Press; Boca Raton: 1984: 01-51