Platelet aggregation and fibrinogen binding in human, rhesus monkey, guinea-pig, hamster and rat blood: activation by ADP and a thrombin receptor peptide and inhibition by glycoprotein IIb/IIIa antagonists

• Published in: Thrombosis and haemostasis Vol. 70; no. 3; p. 531
• Main Authors: Cook, N S, Zerwes, H G, Tapparelli, C, Powling, M, Singh, J, Metternich, R, Hagenbach, A
• Format: Journal Article
• Language: English
• Published: Germany 01-09-1993
• Subjects: Adenosine Diphosphate - pharmacology; Animals; Cricetinae; Fibrinogen - metabolism; Flow Cytometry; Guinea Pigs; Humans; Macaca mulatta; Peptide Fragments - pharmacology; Platelet Activation - drug effects; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Platelet Membrane Glycoproteins - antagonists & inhibitors; Protein Binding; Rats; Species Specificity
• ISSN: 0340-6245
• DOI: 10.1055/s-0038-1649618

Platelet aggregation and fibrinogen binding in whole blood, induced either by ADP or by a 14 amino acid peptide mimicking an N-terminal region of the platelet thrombin receptor (TRP, thrombin receptor activating peptide), have been studied with blood from different species. Aggregation was assessed by counting the number of single platelets in blood before und after addition of the agonist with an automated cell counter. Both ADP (0.02-0.5 microM) and TRP (1-10 microM) were found to be potent agonists of platelet aggregation in human, rhesus monkey and guinea-pig blood, causing a near-maximal aggregatory response within 2 min of agonist addition. In contrast, hamster and rat platelets were much less responsive to both ADP and TRP in terms of the whole blood aggregation. Echistatin, RGDW and a synthetic glycoprotein (GP) IIb/IIIa antagonist, Ro 43-8857, inhibited fibrinogen binding to purified immobilized human GP-IIb/IIIa with IC50's of 1.6, 88 and 11.4 nM, respectively. In whole human blood, the respective IC50's (as determined by flow cytometric analysis of platelet fibrinogen binding) were 4.4, 1700 and 29.5 nM. The affinities of these three compounds for inhibiting fibrinogen binding in whole blood from rhesus monkeys and guinea-pigs were similar to the affinities for human platelets, but with rat blood echistatin, RGDW and Ro 43-8857 were all around 100-fold less potent. Ro 43-8857 was a potent inhibitor of ADP- or TRP-induced platelet aggregation in human, rhesus monkey and guinea-pig whole blood (IC50 of 69-320 nM) but was much less active in hamster blood.