Heparin potentiation of collagen-induced platelet aggregation is related to the GPIIb/GPIIIa receptor and not to the GPIb receptor, as tested by whole blood aggregometry.
To determine whether heparin potentiation of platelet aggregation is related to platelet GP IIb/IIIa and GP Ib receptors, four series of experiments were performed on blood from normal volunteers. In the first experiment pretreatment with the monoclonal antibody 7E3 (MAb 7E3), which antagonizes at the GP IIb/IIIa receptor, potently inhibited the collagen-induced platelet aggregation (p less than 0.001). With heparin added to blood pretreated with MAb 7E3, the aggregation increased (p less than 0.005) to an extent similar to that when only saline was used for pretreatment. In the second experiment, monoclonal antibody 10E5 (MAb 10E5) and peptide RGDS, substances which also antagonize at the GP IIb/IIIa receptor, decreased collagen-induced platelet aggregation to an extent similar to that after pretreatment with MAb 7E3. Following pretreatment with RGDS, heparin increased platelet aggregation (p less than 0.03), while after pretreatment with antibody MAb 10E5 heparin did not enhance platelet aggregation. In the third experiment aurin, an inhibitor of von Willebrand factor and its interaction with the platelet GPIb receptor, decreased platelet aggregation dose-dependently. In the fourth experiment heparin enhanced platelet aggregation to a similar extent (p less than 0.005), regardless of pretreatment of the blood with saline, aurin or monoclonal antibody 6D1 (MAb 6D1), the latter an antagonist at the GP Ib receptor. In conclusion, the potentiation of collagen-induced platelet aggregation by heparin was not inhibited by MAb 7E3, RGDS, aurin or MAb 6D1, but was abolished by MAb 10E5, implying that the heparin effect is related to activation of the platelet GP IIb/IIIa receptor complex.
Chen
J
J
Department of Medicine, Huddinge Hospital, Sweden.
Sylvén
C
C
D000328:Adult; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001312:Aurintricarboxylic Acid / Q000031:analogs & derivatives; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001665:Binding Sites; D003094:Collagen / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D001559:Benzhydryl Compounds; D009842:Oligopeptides; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; C028254:von Willebrand factor receptor; D001312:Aurintricarboxylic Acid; C017037:aurin; D006493:Heparin; D003094:Collagen; C046617:arginyl-glycyl-aspartyl-serine