Effect of Amino Sugars on Platelet Aggregation and on Fibrinogen Binding

Summary

The amino sugars glucosamine, galactosamine and man- nosamine (30 mM) inhibited aggregation of human or rabbit platelets induced by ADP, collagen, thrombin, PAF or high concentrations of sodium arachidonate. ¹²⁵I-fibrinogen binding during ADP-induced aggregation, and release of amine storage granule contents were also inhibited. Increasing the calcium concentration of the suspending medium to 5 mM did not overcome the inhibitory effect on the release reaction.

The amino sugars deaggregated rabbit platelets that had been aggregated by ADP, collagen or thrombin, but deaggregated human platelets readily only when ADP was used as the aggregating agent. Fibrinogen-induced aggregation of chymotrypsin-treated platelets was blocked by the amino sugars. They did not inhibit platelet adherence to a collagen-coated glass surface, nor affect release of granule contents from the adherent platelets. Aggregation and release induced by low concentrations of sodium arachidonate or the divalent cation ionophore A23187 were potentiated, indicating that the effects of the amino sugars on platelets are more complex than simple inhibition of the lectinlike activity that becomes available on the surface of platelets that have undergone the release reaction. One of the effects of the amino sugars, however, is interference with the binding of fibrinogen to platelets. The effects of the amino sugars are shared by other primary amines.

Keywords

Platelet aggregation - Fibrinogen binding - Amino sugars

• References

• 1 Gartner TK, Williams DC, Minion FC, Phillips DR. Thrombin- induced platelet aggregation is mediated by a platelet plasma mem-brane-bound lectin. Science 1978; 200: 1281-1283
• 2 Kinlough-Rathbone RL, Chahil A, Perry DW, Packham MA, Mustard JF. Effect of amino sugars that block platelet lectin activity on fibrinogen binding to washed rabbit or human platelets. Blood 1979; 54 Suppl (Suppl. 01) 249 a
• 3 Bertram J, Ragatz BH, Baldwin W, Iatrides PG. The effects of glucosamine on platelet aggregation. Thromb Res 1981; 23: 301-307
• 4 Jerushalmy Z, Skoza L, Zucker MB, Grant R. Inhibition by guanidine compounds of platelet aggregation induced by adenosine diphosphate. Biochem Pharmacol 1966; 15: 1791-1803
• 5 Ts’ao C, Hart SJ, Krajewski DV, Sorensen PG. Opposite effect of lysine on platelet aggregation induced by arachidonate and by other aggregants. Thromb Haemostas 1982; 48: 78-83
• 6 Houston DS, Gerrard JM, McCrea JM, Glover S, Butler AM. The influence of amines on various platelet responses. Biochim Biophys Acta 1983; 734: 267-273
• 7 Livne A, Gartner TK, Agam G. Inhibition of platelet aggregation and activity of the endogenous platelet lectin by oligoamines. Thromb Haemostas 1983; 50: 132 (Abstr.)
• 8 Gartner TK, Gerrard JM, White JG, Williams DC. Fibrinogen is the receptor for the endogenous lectin of human platelets. Nature 1981; 289: 688-690
• 9 Nachman RL, Leung LL. Complex formation of platelet membrane glycoproteins IIb and IIIa with fibrinogen. J Clin Invest 1982; 69: 263-269
• 10 Packham MA, Guccione MA, Nina M, Kinlough-Rathbone RL, Mustard JF. Effect of Tris on responses of human and rabbit platelets to aggregating agents. Thromb Haemostas 1984; 51: 140-144
• 11 Mustard JF, Perry DW, Ardlie NG, Packham MA. Preparation of suspensions of washed platelets from humans. Br J Haematol 1972; 22: 193-204
• 12 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
• 13 Greenberg JP, Packham MA, Guccione MA, Harfenist EJ, Orr JL, Kinlough-Rathbone RL, Perry DW, Mustard JF. The effect of pretreatment of human or rabbit platelets with chymostrypsin on their responses to human fibrinogen and aggregating agents. Blood 1979; 54: 753-765
• 14 Grant RA, Zucker MB. Effects of chymotrypsin on the release reaction and aggregation of blood platelets. Proc Soc Exp Biol Med 1980; 165: 114-117
• 15 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
• 16 Kinlough-Rathbone RL, Cazenave J-P, Packham MA, Mustard JF. Effect of inhibitors of the arachidonate pathway on the release of granule contents from rabbit platelets adherent to collagen. Lab Invest 1980; 42: 28-34
• 17 Mustard JF, Perry DW, Kinlough-Rathbone RL, Packham MA. Factors responsible for ADP-induced release reaction of human platelets. Am J Physiol 1975; 228: 1757-1165
• 18 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; 7: 693-694
• 19 McFarlane AS. Efficient trace-labelling of proteins with iodine. Nature 1958; 182: 53
• 20 Mustard JF, Packham MA, Kinlough-Rathbone RL, Perry DW, Regoeczi E. Fibrinogen and ADP-induced platelet aggregation. Blood 1978; 52: 453-466
• 21 Harfenist EJ, Packham MA, Mustard JF. Reversibility of the association of fibrinogen with rabbit platelets exposed to ADP. Blood 1980; 56: 189-198
• 22 Kinlough-Rathbone RL, Reimers H-J, Mustard JF, Packham MA. Sodium arachidonate can induce platelet shape change and aggregation which are independent of the release reaction. Science 1976; 192: 1011-1012
• 23 Kinlough-Ratbone RL, Chahil A, Packham MA, Reimers H-J, Mustard JF. Effect of A23,187 on thrombin-degranulated washed rabbit platelets. Thromb Res 1975; 7: 435-449
• 24 Packham MA, Warrior ES, Glynn MF, Senyi AS. Alteration of the response of platelets to surface stimuli by pyrazole compounds. J Exp Med 1967; 126: 171-188
• 25 Mustard JF, Packham MA. Platelet aggregation and the platelet release reaction in thromboembolism. Can Med Assoc J 1970; 103: 859-863
• 26 Ganguly P, Bradford HR. Inhibition of platelet aggregation by primary amines. Evidence for a possible role of membrane-associated calcium Biochim Biophys Acta 1982; 714: 192-199
• 27 Jaffe EA, Leung LL, Nachman RL, Levin RI, Mosher DF. Thrombospondin is the endogenous lectin of human platelets. Nature 1982; 295: 246-248
• 28 Kinlough-Rathbone RL, Mustard JF, Packham MA, Perry DW, Reimers H-J, Cazenave J-P. Properties of washed human platelets. Thromb Haemostas 1977; 37: 291-308
• 29 Peerschke E, Zucker MB, Grant RA, Egan JJ, Johnson MM. Correlation between fibrinogen binding to human platelets and platelet aggregability. Blood 1980; 55: 841-847
• 30 Marguerie GA, Edgington TS, Plow EF. Interaction of fibrinogen with its platelet receptor as part of a multistep reaction in ADP- induced platelet aggregation. J Biol Chem 1980; 255: 154-161
• 31 Kinlough-Rathbone RL, Mustard JF, Perry DW, Dejana E, Cazenave J-P, Packham MA, Harfenist EJ. Factors influencing the deaggregation of human and rabbit platelets. Thromb Haemostas 1983; 49: 162-167
• 32 Feinman RD, Detwiler TC. Absence of a requirement for extracellular calcium for secretion from platelets. Thromb Res 1975; 7: 677-679
• 33 Caen JP, Vainer H, Sultan Y, Lukasiewicz H. Constitutional and acquired abnormalities of platelet aggregation. Ser Haematol 1970; 3: 83-99