Receptors for Platelet Agonists

  • David R. Phillips


Platelet function is initiated by agonist interactions with specific receptors on the membrane surface. A broad spectrum of physiological agonists is capable of activating human platelets. These include a protease (thrombin), an adenine nucleotide (ADP), a structural protein (fibrillar collagen), and α-adrenergic agonists (e.g., epinephrine). Many agents not normally found in blood will also elicit an activation response. These include calcium ionophores (A23187), proteases (trypsin and thermolysin), phorbol esters (e.g., phorbol 12-myristate 13-acetate), lectins (wheat germ agglutinin), and antiplatelet antiserum. A variety of responses can occur, depending on the strength and concentration of the agonist. With a weak agonist such as ADP, platelets will change shape and aggregate. With stronger agonists such as collagen and thrombin, platelets will secrete the contents of their storage organelles in addition to changing shape and aggregating.


Human Platelet Platelet Membrane Fibrillar Collagen Thrombin Receptor Collagen Receptor 
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  1. Adler, J. R., and Handin, R. L, 1979, Solubilization and characterization of a platelet membrane ADP- binding protein,J. Biol. Chem. 254:3866–3872.PubMedGoogle Scholar
  2. Aihara, M., Cooper, H. A., and Wagner, R. H., 1984, Platelet-collagen interactions: Increase in rate of adhesion 37 of fixed washed platelets by factor VIII-related antigen. Blood 63:495–501.PubMedGoogle Scholar
  3. Aktories, K., 1981, Epinephrine inhibits adenylate cyclase and stimulates a GTPase in human platelet membrane via alpha-adrenoceptors, FEBS Lett. 130:235–238.PubMedCrossRefGoogle Scholar
  4. Alexander, R. J., Fenton, II, J W., and Detwiler, T. C., 1983, Thrombin-platelet interactions: An assessment of the roles of saturable and nonsaturable binding in platelet activation. Arch. Biochem. Biophys. 222:266–275.PubMedCrossRefGoogle Scholar
  5. Alexander, R. W., Cooper, B., and Handin, R. I., 1978, Characterization of the human platelet a- adrenergic receptor, J. Clin. Invest. 78:1136–1144.CrossRefGoogle Scholar
  6. Awbry, B. J., Hoak, J. C., and Owen, W. G., 1979, Binding of thrombin to cultured human endothelial cells, J. Biol Chem. 254:4092–4095.Google Scholar
  7. Baker, J. B., Low, D. A., Sinmier, R. L., and Cunningham, D. D., 1980, Protease-Nexin: A cellular component that links thrombin and plasminogen activator and mediates their binding to cells. Cell 21:37–45.PubMedCrossRefGoogle Scholar
  8. Barnathan, E. S., Addonizio, V. P., and Shattil, S. J., 1982, Interaction of verapamil with human platelet receptors. Am. J. Physiol. 242:H19-H23.PubMedGoogle Scholar
  9. Barnes, M. J., Gordon, J. L., and Maclntyre, D. E., 1976, Platelet aggregating activity of type I and type III collagens from human aorta and chicken skin, Biochem. J. 160:647–651.PubMedGoogle Scholar
  10. Bar-Shavit, R., Kahn, A., Fenton, II J. W., and Wilner, G. D., 1983, Chemotactic response of monocytes to thrombin, J. Cell Biol. 96:282–285.PubMedCrossRefGoogle Scholar
  11. Bauer, P. I., Machovich, R., Arányi, P., Káimán, G. B., Eva, C., and Horráth, I., 1983, Mechanism of thrombin binding to endothelial cells. Blood 62:368–372.Google Scholar
  12. Baumgartner, H. R., 1977, Platelet interaction with collagen fibrils in flowing blood. I. Reaction of human platelets with alpha chymotrypsin-digested subendothelium, Thromb. Haemost. 37:1–16.PubMedGoogle Scholar
  13. Beachey, E. H., Chiang, T. M., and Kaug, A. H., 1979, Collagen platelet interaction, in: International Review of Connective Tissue Research, Volume 8, (D. Hall and D. S. Jackson, eds). Academic Press, Inc., New York, pp. 1–21.Google Scholar
  14. Bennett, J. S., Colman, R. F., and Colman, R. W., 1978, Identification of adenine nucleotide binding proteins in human platelet membranes by affinity labeling with 5’-P-fluorosulfonylbenzoyl adenosine, J. Biol. Chem. 253:7346–7354.PubMedGoogle Scholar
  15. Bensusan, H. B., Koh, T. L., Henry, K. G., Murray, B. A., and Culp, L. A., 1978, Evidence that fibronectin is the collagen receptor on platelet membranes, Proc. Natl. Acad. Sci. U.S.A. 75:5864- 5868.PubMedCrossRefGoogle Scholar
  16. Berndt, M. C., and Phillips, D. R., 1981a, Interaction of thrombin with platelets: Purification of the thrombin substrate,Ann. N.Y. Acad. Sci. 370:87–95.PubMedCrossRefGoogle Scholar
  17. Berndt, M. C., and Phillips, D. R., 1981b, Purification and preliminary physicochemical characterization of human platelet membrane glycoprotein V, J. Biol. Chem. 256:59–65.PubMedGoogle Scholar
  18. Berndt, M. C., and Phillips, D. R., 1981c, Platelet membrane proteins: Composition and receptor function, in: Platelets in Biology and Pathology,Volume 2 (J. L. Gordon, ed.), Elsevier/North-Holland Biomedical Press, Amsterdam, pp. 43–75.Google Scholar
  19. Born, G. V. R., 1962, Aggregation of blood platelets by adenosine diphosphate and its reversal,Nature (London) 192 :927–929. CrossRefGoogle Scholar
  20. Born, G. V. R., and Feinberg, H., 1975, Binding of adenosine diphosphate to intact human platelets, J. Physiol. (London) 251:803–816.Google Scholar
  21. Boullin, D. J., Green, A. R., and Price, K. S., 1972, The mechanism of adenosine diphosphate induced platelet aggregation: Binding to platelet receptors and inhibition of binding and aggregation by prostaglandin Gl, J . Physiol 221:415–426.PubMedGoogle Scholar
  22. Brass, L. F., Faile, D., and Bensusan, H. B., 1976, Direct measurement of the plateletxollagen interaction by affinity chromatography on collagen/Sepharose, J. Lab. Clin. Med.87:525–534.PubMedGoogle Scholar
  23. Carney, D. H., and Bergmann, J. S., 1982, 125I-thrombin binds to clustered receptors on noncoated regions of mouse embryo cell surfaces. J. Cell Biol. 95:697–703.PubMedCrossRefGoogle Scholar
  24. Cazenave, J. P., Packham, M. A., and Mustard, J. F., 1973, Adherence of platelets to a collagen-coated surface: Development of a quantative method, J. Lab. Clin. Med. 82:978–990.PubMedGoogle Scholar
  25. Cazenave, J. P., Reimers, H. J., Kinlough-Rathbone, R. L., Packham, M. A., and Mustard, J. F., 1976, Effects of sodium periodate on platelet function, Lab. Invest. 34:471–481.PubMedGoogle Scholar
  26. Chiang, T. M., and Kang, A. H., 1982, Isolation and purification of collagen ai(I) receptor from human platelet membrane, J. Biol. Chem. 257:7581–7586.PubMedGoogle Scholar
  27. Chiang, T. M., and Kang, A. H., 1983, Immunochemical studies of the purified chick skin collagen al(I) chain receptor of human platelets (abstract), Fed. Proc. 42:1368.Google Scholar
  28. Chiang, T. M., Beachy, E. H., and Kang, A. H., 1977, Binding of collagen α 1 chains to human platelets, J. Clin. Invest. 59:405–411.PubMedCrossRefGoogle Scholar
  29. Chen, L. B., and Buchanan, J. M., 1975, Mitogenic activity of blood components. I. Thrombin and prothrombin, Proc. Natl. Acad. Sci. U.S.A. 72:131–135.PubMedCrossRefGoogle Scholar
  30. Clare, K. A., and Scrutton, M. C., 1984, The role of Ca2+uptake in the response of human platelets to adrenaline and to l-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor),Eur. J. Biochem. 140:129–136.PubMedCrossRefGoogle Scholar
  31. Colman, R. W., Figures, W. R., Colman, R. F., Morinelli, T. A., Niewiarowski, S., and Mills, D. C. B., 1980, Identification of two distinct adenosine diphosphate receptors in human platelets, Trans. Assoc. Am. Physicians XCIII:305–316.Google Scholar
  32. Connolly, T. M., and Limbird, L. E., 1983, The influence of Na+on the α2-adrenergic receptor system of human platelets. A method for removal of extraplatelet Na+. Effect of Na+removed on aggregation, secretion, and cAMP accumulation, J. Biol. Chem. 258:3907–3912.PubMedGoogle Scholar
  33. Davey, M. G., and Lüscher, E. F., 1967, Actions of thrombin and other coagulant and proteolytic enzymes on blood platelets, Nature (London) 216:857–858.CrossRefGoogle Scholar
  34. DeLean, A., Stadel, J. M., and Lefkowitz, R. J., 1980, A ternary complex model explains the agonist- specific binding properties of the adenylate cyclase-coupled b-adrenergic receptor, J. Biol. Chem. 255:7108–7117.Google Scholar
  35. Detwiler, T. C., and Feinman, R. D., 1973a, Kinetics of the thrombin-induced release of calcium (II) by platelets, Biochemistry 12:282–289.PubMedCrossRefGoogle Scholar
  36. Detwiler, T. C., and Feinman, R. D., 1973b, Kinetics of the thrombin-induced release of adenosine triphosphate by platelets. Comparison with release of calcium. Biochemistry 12:2462–2468.PubMedCrossRefGoogle Scholar
  37. Detwiler, T. C., and Huang, E. M., 1985, Stimulus-response coupling mechanisms, in: Biochemistry of Platelets(D. R. Phillips and M. Shuman, eds.), Academic Press, New York (in press).Google Scholar
  38. Esmon, N. L., Carroll, R. C., and Esmon, C. T., 1983, Thrombomodulin blocks the ability of thrombin to activate platelets, J. Biol. Chem. 258:12238–12242.PubMedGoogle Scholar
  39. Eyre, D. R., 1980, Collagen: Molecular diversity in the body’s protein scaffold. Science 207:1315–1322.PubMedGoogle Scholar
  40. Fauvel, F., Legrand, Y. J., and Caen, J. P., 1978a, Platelet adhesion to type I collagen and alpha 1 (1)3 trimers: Involvement of the C-terminal alpha 1(1) CB6A peptide, Thrombin. Res. 12:273–285.CrossRefGoogle Scholar
  41. Fauvel, F., Legrand, Y. J., Bentz, H., Fietzek, P. P., Kuhn, K., and Caen, J. P., 1978b, Platelet collagen interaction. Adhesion of human blood platelets to purified CB-4 peptide from type III collagen, Thromb. Res. 12:841–850.PubMedCrossRefGoogle Scholar
  42. Fenton, II J. W., Walz, D. A., and Finlayson, J. S., 1977, Human thrombins, in: Chemistry and Biology of Thrombin(R. L. Lundblad, J. W. II Fenton,, and K. G. Mann, eds.), Ann Arbor Science Publishers, Inc., Ann Arbor, MI, pp. 43–70.Google Scholar
  43. Figures, W. R., Niewiarowski, S., Morinelli, T. A., Colman, R. F., and Colman, R. W., 1981, Affinity labeling of a human platelet membrane protein with 5’-P-fluorosulfonylbenzoyl adenosine. Concomitant inhibition of ADP-induced platelet aggregation and fibrinogen receptor exposure, J. Biol. Chem. 256:7789–7795.PubMedGoogle Scholar
  44. Fujimura, K., Maehama, S., and Kuramoto, A., 1980, The effect of protease on platelet plasma membrane; proteins. The mode of thrombin action on glycoprotein I and V and on platelet functions, Acta Haematol Jpn. 43:198–207.Google Scholar
  45. Furie, M., and Rifkin, D. B., 1980, Proteolytically derived fragments of human plasma fibronectin and their localization within the intact molecule, J. Biol. Chem. 255:3134–3140.PubMedGoogle Scholar
  46. Gaarder, A., Jonsen, J., Laland, S., Hellem, A., and Owren, P. A., 1961, Adenosine diphosphate in red cells as a factor in the adhesiveness of human blood platelets. Nature (London) 192:531–532.CrossRefGoogle Scholar
  47. Ganguly, P., and Fossett, N. G., 1981, Inhibition of thrombin-induced platelet aggregation by a derivative of wheat germ agglutinin. Evidence for a physiologic receptor of thrombin in human platelets. Blood 57:343–352.PubMedGoogle Scholar
  48. Ganguly, P., and Gould, N. L., 1979, Thrombin receptors of human platelets. Thrombin binding and antithrombin properties, Br. J. Haematol. 42:137–145.PubMedCrossRefGoogle Scholar
  49. Ganguly, P., and Sonnichsen, W. J. 1976, Binding of thrombin to human platelets and its possible significance, Br. J. Haematol. 34:291–301PubMedCrossRefGoogle Scholar
  50. Gear, A. R. L., and Burke, D., 1983, Thrombin-induced secretion of serotonin from platelets can occur in; seconds, Blood 60:1231–1234.Google Scholar
  51. George, J. N., Lyons, R. M., and Morgan, R. K., 1980, Membrane changes associated with platelet activation. Exposure of actin on the platelet surface after thrombin-induced secretion,J. Clin. Invest. 66:1–9.PubMedCrossRefGoogle Scholar
  52. George, J. N., Nurden, A. T., and Phillips, D. R., 1984, Molecular defects in interactions of platelets with the vessel wall, N. Engl. J. Med. 311:1084–1098.PubMedCrossRefGoogle Scholar
  53. Glenn, K. C., Carney, D. H., Fenton, II J. W., and Cunningham, D. D., 1980, Thrombin active site regions required for fibroblast receptor binding and initiation of cell division, J. Biol. Chem. 255:6609- 6616.PubMedGoogle Scholar
  54. Goodnough, L. T., and Saito, H., 1982, Specific binding of thrombin by human peripheral blood monocytes: Possible role in the clearance of activated factors from the circulation, J. Lab. Clin. Med. 99:873–884.PubMedGoogle Scholar
  55. Gospodarowicz, D., Brown, K. D., Birdwell, C. R., Zetter, B. R., 1978, Control of proliferation of human vascular endothelial cells. Characterization of the response of human umbilical vein endothelial cells to fibroblast growth factor, epidermal growth factor, and thrombin, J. Cell Biol. 77:774–788.PubMedCrossRefGoogle Scholar
  56. Grant, J. A., and Scrutton, M. C., 1979, Novel α2-adrenoreceptors primarily responsible for inducing human platelet aggregation. Nature (London) 277:659–661.CrossRefGoogle Scholar
  57. Grette, K., 1962, Studies on the mechanism of thrombin-catalyzed hemostatic reactions in blood platelets, Acta Physiol. Scand.56 (Suppl.) 195:1–93.Google Scholar
  58. Hagen, I., Brosstad, F., Solum, N. O., and Korsmo, R., 1981, Crossed Immunoelectrophoresis using inmiobilized thrombin in intermediate gel. A method for demonstration of thrombin-binding platelet proteins, J. Lab. Clin. Med. 97:213–220.PubMedGoogle Scholar
  59. Haslam, R. J., and Cusack, N. J., 1981, Blood platelet receptors for ADP and for adenosine, in: Purinergic Receptors (Receptors and Recognition,Series B. Volume 12) (G. Bumstock, ed.), Chapman and Hall, London, pp. 223–285.Google Scholar
  60. Haslam, R. J., and Rossen, G. M., 1975, Effects of adenosine on levels of adenosine 3’:5’-cyclic monophosphate in human blood platelets in relation of adenosine incorporation and platelet aggregation.Mol. Pharmacol. 11:528–544.PubMedGoogle Scholar
  61. Henriksen, R. A., and Brotherton, A. F. A., 1983, Evidence that activation of platelets and endothelium by thrombin involves distinct sites of interaction. Studies with the dysthrombin, thrombin Quick I, J. Biol. Chem. 258:13717–13721.PubMedGoogle Scholar
  62. Hoffman, B. B., Michel, T., Kilpatrick, D. M., Lefkowitz, R. J., Tolbert, M. E. M., Gilman, H., and Fain, J. N., 1980, Agonist versus antagonist binding to α-adrenergic receptors, Proc. Natl. Acad. Sci. U.S.A. 77:4569–4578.PubMedCrossRefGoogle Scholar
  63. Holderbaum, D., Culp, L. A., Bensusan, H. B., and Gershman, H., 1982, Platelet stimulation by anti-fibronectin antibodies requires the Fc region of antibody, Proc. Natl. Acad. Sci. U.S.A.79:6537–6540.PubMedCrossRefGoogle Scholar
  64. Holmsen, H., and Weiss, H. J., 1979, Secretable storage pools in platelets,Annu. Rev. Med. 30:119–134.PubMedCrossRefGoogle Scholar
  65. Holmsen, H., Dangelmaier, C. A., and Holmsen, H.-K., 1981, Thrombin-induced platelet responses differ in requirement for receptor occupancy, J. Biol. Chem. 256:9393–9396.PubMedGoogle Scholar
  66. Huang, E. M., and Detwiler, T. C., 1980, Reassessment of the evidence for the role of secreted ADP in biphasic platelet aggregation. J. Lab. Clin. Med. 95:59–68.PubMedGoogle Scholar
  67. Isaacs, J. D., Savion, N., Gospodarowicz, D., Fenton, II J. W., and Shuman, M. A., 1981a, Covalent binding of thrombin to specific sites on corneal endothelial cells.Biochemistry 20:398–403.PubMedCrossRefGoogle Scholar
  68. Isaacs, J. D., Savion, N., Gospodarowicz, D., and Shuman, M. A., 1981b, Effect of cell density on thrombin binding to a specific site on bovine vascular endothelial cells, J. Cell Biol. 90:670–674.PubMedCrossRefGoogle Scholar
  69. Jakobs, K. H., 1983, Determination of the tum-off reaction for the epinephrine-inhibited human platelet adenylate cyclase, Eur. J. Biochem. 132:125–130.PubMedCrossRefGoogle Scholar
  70. Jakobs, K. H., Saur, W., and Shultz, G., 1978, Characterization of alpha- and beta-adrenergic receptors linked to human platelet adenylate cyclase. Arch. Pharmacol. 302:285–291.CrossRefGoogle Scholar
  71. Jamieson, G. A., and Okumura, T., 1978, Reduced thrombin binding and aggregation in Bemard-Soulier platelets, J. Clin. Invest. 61:861–864.PubMedCrossRefGoogle Scholar
  72. Kang, A. H., Beachey, E. H., and Katzman, R. L., 1974, Interaction of an active glycopeptide from chick skin collagen (α-l-CB5) with human platelets, J. Biol. Chem. 249:1054–1059.PubMedGoogle Scholar
  73. Katzman, R. L., Kang, A. H., and Beachey, E. H., 1973, Collagen-induced platelet aggregation: Involvement of an active glycopeptide fragment (αl-CB5), Science 181:670–672.PubMedCrossRefGoogle Scholar
  74. Knupp, C. L., and White II G. C., 1981, Effect of active site-modified thrombin on the hydrolysis of platelet-associated glycoprotein V by native thrombin, Blood 58:198a.Google Scholar
  75. Kramer, R. M., Jakubowski, J. A., Vaillancourt, R., and Deykin, D., 1982, Effect of membrane cholesterol on phospholipid metabolism in thrombin-stimulated platelets. Enhanced activation of platelet phospholipase(s) for liberation of arachidonic acid, J. Biol. Chem. 257:6844–6849.PubMedGoogle Scholar
  76. Lahav, J., Schwartz, M. A., and Hynes, R. O., 1982, Analysis of platelet adhesion using a radioactive chemical crosslinking reagent: Interaction of thrombospondin with fibronectin and collagen, Cell 31:253–262.PubMedCrossRefGoogle Scholar
  77. Larsen, N. E., and Simons, E. R., 1981, Preparation and application of a photoreactive thrombin analog: Binding to human platelets. Biochemistry 20:4144–4147.CrossRefGoogle Scholar
  78. Larsen, N. E., Home, W. C., and Simons, E. R., 1979, Platelet interaction with active and TLCK- inactivated α-thrombin,Biochem. Biophys. Res. Commun. 87:403–409.PubMedCrossRefGoogle Scholar
  79. Legrand, C., Dubemard, V, and Caen, J., 1980, Further characterization of human platelet ADP binding sites using 5’ AMP. Demonstration of a highly reactive population of sites, Biochem. Biophys. Res. Commun. 96:1–9.PubMedCrossRefGoogle Scholar
  80. Legrand, Y. J., Kamiguian, A., LeFrancier, P., Fauvel, F., and Caen, J. P., 1980, Evidence that a collagen- derived nonapeptide is a specific inhibitor of platelet-collagen interaction, Biochem. Biophys. Res. Commun. 96:1579–1585.PubMedCrossRefGoogle Scholar
  81. Leven, R. M., Mullikin, W. H., and Nachmias, V. T., 1983, Role of sodium in ADP- and thrombin-induced megakaryocyte spreading, J. Cell Biol. 96:1234–1240.PubMedCrossRefGoogle Scholar
  82. Levine, J. D., Harlan, J. M., Harker, L. A., Joseph, M. L., and Counts, R. B., 1982, Thrombin-mediated release of Factor VIII antigen from human umbilical vein endothelial cells in culture. Blood 60:531- 534.PubMedGoogle Scholar
  83. Lips, J. P. M., Sixma, J. J., and Schiphorst, M. E., 1980a, Binding of adenosine diphosphate to human blood platelets and to isolated blood platelet membranes, Biochim. Biophys. Acta 628:451–467.PubMedCrossRefGoogle Scholar
  84. Lips, J. P. M., Sixma, J. J., and Schiphorst, M. E., 1980b, The effect of ticlopidine administration to humans on the binding of adenosine diphosphate to blood platelets,Thromb. Res. 17:19–27.PubMedCrossRefGoogle Scholar
  85. Lollar, P., Hoak, J. C., and Owen, W. G., 1980, Binding of thrombin to cultured human endothelial cells. Nonequilibrium aspects,J. Biol. Chem. 255:10279–10283.PubMedGoogle Scholar
  86. Low, D. A., Scott, R. W., Baker, J. B., and Cunningham, D. D., 1982, Cells regulate their mitogenic response to thrombin through release of protease nexin. Nature (London) 298:476–478.CrossRefGoogle Scholar
  87. Lyman, B., Rosenberg, L., and Karpatkin, S., 1971, Biochemical and biophysical aspects of human platelet adhesion to collagen fibers, J. Clin. Invest. 50:1854–1863.PubMedCrossRefGoogle Scholar
  88. Macfarlane, D. E., and Mills, D. C. B., 1975, The effects of ATP on platelets: Evidence against the central role of released ADP-primary aggregation. Blood 46:309–320.PubMedGoogle Scholar
  89. Macfarlane, D. E., and Stump, D. C., 1982, Parallel observation of the occupancy of the alpha-2 adrenergic receptor in intact platelets and its ability to inhibit adenylate cyclase, Mol. Pharmacol. 22:574–579.PubMedGoogle Scholar
  90. Macfariane, D. E., Srivastova, P., and Mills, D. C. B., 1979, 2-Methylthioadenosine-5’-diphosphate (2MeSADP), a high affinity probe for ADP receptors on the human platelet (abstract), Thromb. Haemost. 42:185.Google Scholar
  91. Macfarlane, D. E., Mills, D. C. B., and Srivastova, P. C., 1982, Binding of 2-azidoadenosine[beta-32p] diphosphate to the receptor on intact human blood platelets which inhibits adenylate cyclase. Biochemistry21:544–549.PubMedCrossRefGoogle Scholar
  92. Macfarlane, D. E., Srivastava, P. C., and Mills, D. C. B., 1983, 2-Methylthioadenosine [b-32p] diphosphate. An agonist and radioligand for the receptor that inhibits the accumulation of cyclic AMP in intact blood platelets, J. Clin. Invest. 71:420–428.PubMedCrossRefGoogle Scholar
  93. Mannherz, T. G., and Goody, R. S., 1976, Proteins of contractile systems, Annu. Rev. Biochem. 45:427- 465.PubMedCrossRefGoogle Scholar
  94. Martin, B. M., Feinman, R. D., and Detwiler, T. C., 1975, Platelet stimulation by thrombin and other proteases. Biochemistry 14:1308–1314.PubMedCrossRefGoogle Scholar
  95. McGowan, E. B., Duig, A., and Detwiler, T. C., 1983, Correlation thrombin-induced glycoprotein V hyrolysis and platelet activation, J. Biol Chem. 258:11243–11248.PubMedGoogle Scholar
  96. Meyer, F. A., and Weisman, Z., 1978, Adhesion of platelets to collagen: The nature of the binding site from competitive inhibition studies, Thromb. Res. 12:431–436.PubMedCrossRefGoogle Scholar
  97. Michel, T., Hoffman, B. B., and Lefkowitz, R. J., 1980, Differential regulation of the α2-adrenergic receptor by Na+and guanine nucleotides. Nature (London) 288:709–711.CrossRefGoogle Scholar
  98. Michel, T., Hoffman, B. B., Lefkowitz, R. J., and Caron, M. G., 1981, Different sedimentation properties of agonist- and antagonist-labelled platelet alpha 2 adrenergic receptors, Biochem. Biophys. Res. Commun. 100:1131–1136.PubMedCrossRefGoogle Scholar
  99. Miletich, J. P., Jackson, C. M., and Majerus, P. W., 1978, Properties of the Factor Xa binding site on human platelets, J. Biol. Chem. 253:6908–6916.PubMedGoogle Scholar
  100. Mills, D. C. B., and Macfarlane, D. E., 1976, Platelet receptors, in: Platelets in Biology and Pathology(J. L. Gordon, ed.), Elsevier/North Holland Biomedical Press, Amsterdam, pp. 159–202.Google Scholar
  101. Mills, D. C. B., and Macfarlane, D. E., 1977, Attempts to define a platelet ADP receptor with203Hg-p-mercuribenzene sulfonate (MES) (abstract),Thromb. Haemost. 38:82.Google Scholar
  102. Mills, D. C. B., and Roberts, G. C. K., 1967, Effects of adrenaline on human blood platelets, J. Physiol.(London) 193:443–453.Google Scholar
  103. Mosher, D. F., and Vaheri, A., 1978, Thrombin stimulates the production and release of a major surface- associated glycoprotein (fibronectin) in cultures of human fibroblasts, Exp. Cell Res. 112:323–334.PubMedCrossRefGoogle Scholar
  104. Mosher, D. F., Vaheri, A., Choate, J. J., and Gahmberg, C. G., 1979, Action of thrombin on surface glycoproteins of human platelets, Blood 53:437–445.PubMedGoogle Scholar
  105. Moss, M., Wiley, H. S., Fenton, II J. W, and Cunningham, D. D., 1983, Photoaffmity labeling of specific α-thrombin binding sites on Chinese hamster lung cells, J. Biol. Chem. 258:3996–4002.PubMedGoogle Scholar
  106. Motulsky, H. J., and Insel, P. A., 1983, Influence of sodium on the α2-adrenergic receptor system of human platelets. Role for intraplatelet sodium in receptor binding, J. Biol. Chem. 258:3913–3919.PubMedGoogle Scholar
  107. Mürer, E. H., 1972, Factors influencing the initiation and the extrusion phase of the platelet release reaction, Biochim. Biophys. Acta 261:435–443.CrossRefGoogle Scholar
  108. Nachman, R. L., and Ferris, B., 1974, Binding of adenosine diphosphate by isolated membranes from human platelets, J. Biol. Chem. 249:704–710.PubMedGoogle Scholar
  109. Nesheim, M. E., Taswell, J. B., and Mann, K. G., 1979, The contribution of bovine Factor V and Factor Va to the activity of prothrombrinase,J. Biol. Chem. 254:10952–10962.PubMedGoogle Scholar
  110. Newman, K. D., Williams, L. T., Bishopric, N. H., and Lefkowitz, R. J., 1978, Identification of α- adrenergic receptors in human platelets by [3H]dihydroergocryptine binding, J. Clin. Invest. 61:395- 402.PubMedCrossRefGoogle Scholar
  111. O’Brien, J. R., 1963, Some effects of adrenalin and anti-adrenaline compounds on platelets in vitroand in vivo, Nature (London) 200:163–164. CrossRefGoogle Scholar
  112. Okumura, T., and Jamieson, G. A., 1976, Platelet glycocalicin. A single receptor for platelet aggregation induced by thrombin or ristocetin, Thromb. Res. 8:701–706.PubMedCrossRefGoogle Scholar
  113. Okumura, T., Hasitz, M., and Jamieson, G. A., 1978, Platelet glycocalicin. Interaction with thrombin and role as thrombin receptor of the platelet surface, J. Biol. Chem. 253:3435–3443.PubMedGoogle Scholar
  114. Owen, N. E., Feinberg, H., and LeBreton, G. C., 1980, Epinephrine induces Ca2+uptake in human blood platelets.Am. J. Physiol. 239:H483-H488.PubMedGoogle Scholar
  115. Owen, W. G., and Esmond, C. T., 1981, Functional properties of an endothelial cell cofactor from thrombin-catalyzed activitation of protein C, J. Biol. Chem. 256:5532–5535.PubMedGoogle Scholar
  116. Parise, L. V., Venton, D. L., and LeBreton, G. C., 1984, Arachidonic acid-induced platelet aggregation is mediated by a thromboxane A2/prostaglandin H2receptor interaction, J. Pharmacol Exp. Ther. 228:240–244.PubMedGoogle Scholar
  117. Phillips, D. R., 1972, Effects of trypsin on the exposed polypeptides and glycoproteins in the human platelet membrane. Biochemistry11:4582–4588.PubMedCrossRefGoogle Scholar
  118. Phillips, D. R., 1974, Thrombin interaction with human platelets. Potentiation of thrombin-induced aggregation and release by inactivated thrombin, Thromb. Diath. Haemorrh. 32:207–215.PubMedGoogle Scholar
  119. Phillips, D. R., 1980, An evaluation of membrane glycoproteins in platelet adhesion and aggregation, in: Progress in Hemostasis and Thrombosis, Volume 5 (T. H. Spaet, ed.), Grune and Stratton, New York, pp. 81–109.Google Scholar
  120. Phillips, D. R., and Agin, P. P., 1977, Platelet plasma membrane glycoproteins. Identification of a proteolytic substrate for thrombin, Biochem. Biophys. Res. Commun. 75:940–947.PubMedCrossRefGoogle Scholar
  121. Phillips, D. R., Jennings L K., and Prasanna, H. R., 1980, Ca2+-mediated association of Glycoprotein G (thrombin-sensitive protein, thrombospondin) with human platelets, J. Biol. Chem. 255:11629–11632.PubMedGoogle Scholar
  122. Plow, E. F., and Ginsberg, M. H., 1981, Specific and saturable binding of plasma fibronectin to thrombin- stimulated platelets, J. Biol Chem. 256:9477–9482.PubMedGoogle Scholar
  123. Plow, E. F., Birdwell, C., and Ginsberg, M. H., 1979, Identification and quantitation of platelet-associated fibronectin antigen, J. Clin. Invest. 63:540–543.PubMedCrossRefGoogle Scholar
  124. Rodbell, M., Lin, M. C., Solomon, Y., Londos, C., Harwood, J. P., Martin, B. R., Nendell, M., and Herman, M., 1975, Role of adenine and guanine nucleotides in the activity and response of adenylate cyclase systems to hormones: Evidence for multisite transition states. Adv. Cyclic Nucleotide Res. 5:3-29.PubMedGoogle Scholar
  125. Rogers, G. M., and Shuman, M. A., 1983, Prothrombin is activated on vascular endothelial cells by Factor X and calcium, Proc. Natl Acad. Sci. U.S.A. 80:7001–7005.CrossRefGoogle Scholar
  126. Ruggeri, Z. M., DeMarco, L., Gatti, L., Bader, R., and Montgomery, R. R., 1983, Platelets have more than one binding site for von Willebrand factor, J. Clin. Invest. 72:1–12.PubMedCrossRefGoogle Scholar
  127. Ruoslahti, E., Hayman, E. G., Kuusela, P., Shively, J. E., and Engvall, E., 1979, Isolation of a tryptic fragment containing the collagen-binding site of plasma fibronectin, J. Biol Chem.254:6054–6059.PubMedGoogle Scholar
  128. Salzman, E. W., and Chambers, D. A., 1965, Incorporation by blood platelets of adenosine diphosphate labelled with carbon-14, Nature (London) 206:727–728.CrossRefGoogle Scholar
  129. Salzman, E. W., Kensler, P. C., and Levine, L., 1972, Cyclic 3’,5’-adenosine monophosphate in human blood platelets. IV. Regulatory role of cyclic AMP in platelet function, Ann. N.Y. Acad. Sci.201:61- 71.PubMedCrossRefGoogle Scholar
  130. Santoro, S. A., and Cowan, J. F., 1982, Adsorption of von Willebrand factor by fibrillar collagen. Implications concerning the adhesion of platelets to collagen. Collagen Relat. Res. 2:31–44.Google Scholar
  131. Santoro, S. A., and Cunningham, L. W., 1977, Collagen-mediated platelet aggregation. Evidence for multivalent interactions of intermediate specificity between collagen and platelets, J. Clin. Invest. 60:1054–1060.PubMedCrossRefGoogle Scholar
  132. Santoro, S. A., and Cunningham, L. W., 1979, Fibronectin and the multiple interaction model for platelet- collagen adhesion,Proc. Natl Acad. Sci. U.S.A. 76:2644–2648.PubMedCrossRefGoogle Scholar
  133. Santoro, S. A., and Cunningham, L. W., 1981, The interaction of platelets with collagen, in: Platelets in Biology and Pathology,Volume 2 (J. L. Gordon, ed.), Elsevier/North-Holland Biomedical Press, Amsterdam, pp. 249–264.Google Scholar
  134. Shuman, M. A., Botney, M., and Fenton, II J. W., 1979, Thrombin-induced platelet secretion. Further evidence for a specific pathway, J. Clin. Invest. 63:1212–1218.CrossRefGoogle Scholar
  135. Smith, S. K., and Limbird, L. E., 1981, Solubilization of human platelet α-adrenogenic receptors: Evidence that agonist occupancy of the receptor stabilizes receptor-effector interactions, Proc. Natl Acad. Sci. U.S.A. 78:4026–4030.PubMedCrossRefGoogle Scholar
  136. Snider, R. M., and Richelson, E., 1983, Thrombin stimulation of guanosine 3’,5’-monophosphate formation in murine neuroblastoma cells (Clone NIE-115), Science 221:566–568.PubMedCrossRefGoogle Scholar
  137. Steer, M. L., and Atlas, D., 1982, Demonstration of human platelet b-adrenergic receptors using 125I-unlabeled cyanopindolol and 125I-labeled hydroxybenzylpindolol, Biochim. Biophys. Acta 686:240–244.PubMedCrossRefGoogle Scholar
  138. Steer, M. L., and Wood, A., 1979, Regulation of human platelet adenylate cyclase by epinephrine, prostaglandin E1, and gaunine nucleotides. Evidence for separate guanine nucleotide sites mediating stimulation and inhibition,J. Biol Chem. 254:10791–10797.PubMedGoogle Scholar
  139. Tam, S. W., and Detwiler, T. C., 1978, Binding of thrombin to human platelet plasma membranes, Biochim. Biophys. Acta 543:194–201.PubMedCrossRefGoogle Scholar
  140. Tandon, N., Harmon, J. T., Rodbard, D., and Jamieson, G. A., 1983, Thrombin receptors define responsiveness of cholesterol-modified platelets,J. Biol. Chem. 258:11840–11845.PubMedGoogle Scholar
  141. Taylor, D. G., Mapp, R. J., and Crawford, N., 1975, The identification of actin associated with pig platelet membranes and granules, Biochem. Soc. Trans. 3:161–164.PubMedGoogle Scholar
  142. Tollefsen, D. M., and Majerus, P. W., 1976, Evidence for a single class of thrombin-binding sites on human platelets. Biochemistry 15:2144–2149.PubMedCrossRefGoogle Scholar
  143. Tollefsen, D. M., Feagler, J. R., and Majerus, P. W., 1974, The binding of thrombin to the surface of human platelets, J. Biol. Chem. 249:2646–2651.PubMedGoogle Scholar
  144. Tracy, P. B., Rohrbach, M. S., and Mann, K. G., 1983, Functional prothrombinase complex assembly on isolated monocytes and lymphocytes, J. Biol. Chem. 258:7264–7267.PubMedGoogle Scholar
  145. Tsai, B.-S., and Lefkowitz, R. J., 1978, Agonist-specific effects of monovalent and divalent cations on adenylate cyclase-coupled alpha adrenergic receptors in rabbit platelets, Mol. Pharmacol. 4:540–548.PubMedGoogle Scholar
  146. Tsai, B.-S., and Lefkowitz, R. J., 1979, Agonist-specific effects of guanine nucleotides on alpha-adrenergic receptors in human platelets, Mol. Pharmacol. 16:61–68.PubMedGoogle Scholar
  147. Wallace, W. C., and Bensusan, H. B., 1980, Protein phosphorylation in platelets stimulated by immobilized thrombin at 37° and 4°C, J. Biol. Chem. 255:1932–1937.PubMedGoogle Scholar
  148. Weksler, B. B., Ley, C. W., Jaffe, E. A., 1978, Stimulation of endothelial cell prostacyclin production by thrombin, trypsin and the ionophore A23187, J. Clin. Invest. 62:923–930.PubMedCrossRefGoogle Scholar
  149. White, II G. C., Workman, E. F., Jr., and Lundblad, R. L., 1977, Platelet-thrombin interactions. The platelet as a substrate for thrombin, in: Chemistry and Biology of Thrombin(R. L. Lundblad, J. W. II Fenton, and K. G. Mann, eds.), Ann Arbor Science Publishers, Inc., Ann Arbor, MI, pp. 479–498.Google Scholar
  150. White, G. C., Lundblad, R. L., and Griffith, M. J., 1981, Structure-function relations in platelet-thrombin reactions. Inhibition of platelet-thrombin interactions by lysine modification, J. Biol. Chem. 256:1763–1766.PubMedGoogle Scholar
  151. Williams, L. T., Mullikin, D., and Lefkowitz, R. J., 1976, Identification of alpha-adrenergic receptors in uterine smooth muscle membranes by [3H]dihydroergocryptine binding, J. Biol. Chem. 251:6915- 6923.PubMedGoogle Scholar
  152. Workman, Jr., E. F., White,II G. C., and Lundblad, R. L., 1977, Structure-function relationships in the interaction of α-thrombin with blood platelets, J. Biol. Chem. 252:7118–7123.PubMedGoogle Scholar
  153. Zucker, M. B., Broekman, M. J., and Kaplan, K. L., 1979a, Factor Vlll-related antigen in human blood platelets. Localization and release by thrombin and collagen, J. Lab. Clin. Med. 94:675–682.PubMedGoogle Scholar
  154. Zucker, M. B., Mosesson, M. W., Broekman, M. J., and Kaplan, K. L., 1979b, Release of platelet fibronection (cold-insoluble globulin) from alpha granules induced by thrombin or collagen; lack of requirement for plasma fibronectin in ADP-induced platelet aggregation.Blood 54:8–12PubMedGoogle Scholar

Copyright information

© Plenum Press New York and London 1985

Authors and Affiliations

  • David R. Phillips
    • 1
  1. 1.Gladstone Foundation Laboratories for Cardiovascular Disease, Cardiovascular Research Institute, and Department of PathologyUniversity of California, San FranciscoSan FranciscoCaliforniaUSA

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