title: Differential ability of agonists to express distinct pools of fibrinogen (GpIIb/IIIa) receptors which can mediate the aggregation of human platelets.
abstract: We have investigated the effect of two procedures that modify human platelet surface membrane glycoprotein (Gp) IIb and IIIa complexes upon whole blood platelet aggregation to a range of agonists. (A) Irreversible disruption of complexes by temporary (30 min) Ca2+-deprivation with EGTA at 37 degrees C. (B) Binding of a monoclonal antibody M148 to the complex. EGTA exposure abolished aggregation to ADP, adrenaline and PAF. In contrast, full aggregation curves to collagen and U-46619 could still be established. EGTA exposure reduced M148 binding to platelets by 80%. Excess M148 abolished aggregation to ADP, PAF, collagen and U-46619. However, upon removal of unbound antibody from platelets full aggregation curves to collagen and U-46619 but not to ADP and PAF could be re-established. Thus human platelet aggregation to ADP, PAF and adrenaline appears absolutely dependent upon surface membrane GpIIb/IIIa complexes. In contrast, collagen and U-46619 cause expression of an additional distinct pool of Gp complexes inaccessible to EGTA and M148 in unstimulated platelets which is intimately involved in aggregation to these agonists.
authors.affiliation: Department of Cardiovascular Pharmacology, Glaxo Group Research Ltd, Ware, Hertfordshire, UK.
authors.forename: I S
authors.initials: IS
authors.lastname: Watts
authors.forename: R J
authors.initials: RJ
authors.lastname: Keery
authors.forename: P
authors.initials: P
authors.lastname: Lumley
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D003094:Collagen / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013696:Temperature
chemical_list: D000911:Antibodies, Monoclonal; D010980:Platelet Membrane Glycoproteins; D011450:Prostaglandin Endoperoxides, Synthetic; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D004837:Epinephrine