Comparison of common platelet receptors between the chacma baboon (Papio ursinus) and human for use in pre-clinical human-targeted anti-platelet studies.

Publisher: Informa Healthcare Country of Publication: England NLM ID: 9208117 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1369-1635 (Electronic) Linking ISSN: 09537104 NLM ISO Abbreviation: Platelets Subsets: MEDLINE

Publication: London : Informa Healthcare
Original Publication: Edinburgh ; New York : Churchill Livingstone, c1990-

Blood Platelets/*drug effects ; Blood Platelets/*metabolism ; Platelet Aggregation Inhibitors/*pharmacology ; Platelet Membrane Glycoproteins/*metabolism ; Receptors, Cell Surface/*metabolism; Adenosine Diphosphate/pharmacology ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Arachidonic Acid/pharmacology ; Drug Evaluation, Preclinical ; Flow Cytometry ; Humans ; Male ; Papio ursinus ; Platelet Aggregation/drug effects ; Platelet Membrane Glycoproteins/chemistry ; Platelet Membrane Glycoproteins/genetics ; Receptors, Cell Surface/chemistry ; Receptors, Cell Surface/genetics ; Receptors, Purinergic P2/chemistry ; Receptors, Purinergic P2/genetics ; Receptors, Purinergic P2/metabolism ; Ristocetin/pharmacology

Anti-platelet agents play a central part in the treatment and prevention of acute thrombotic events. Discriminating animal models are needed for the development of novel agents. The chacma baboon has been extensively used as a model to evaluate anti-platelet agents. However, limited data exist to prove the translatability of this species to humans. We aimed to determine the suitability of the chacma baboon in preclinical human targeted GPIIb/IIIa, GPIbα and P2Y12 studies. Light-transmission platelet aggregometry (LTA), whole blood impedance aggregometry, receptor number quantification and genomic DNA sequencing were performed. Baboon ADP and arachidonic acid-induced LTA aggregation results differed significantly from human values, even at increased concentrations. LTA ristocetin-induced agglutination was comparable between species, but baboon platelets needed twice the concentration of ristocetin to elicit a similar response. Citrated baboon blood had significantly less aggregation than humans when evaluated with impedance aggregometry. However, hirudinised baboon whole blood gave similar aggregation as humans at the same agonist concentrations. GPIIb, GPIIIa and GPIbα numbers were significantly more on the baboon platelets. None of the amino acids deemed vital for receptor function, ligand binding or receptor inhibition, were radically different between the species. However, a conservative change in a calcium-binding region of GPIIb may render the baboon platelets more sensitive to calcium-binding agents. The chacma baboon may be used for the evaluation of human-targeted GPIIb/IIIa-, GPIbα- and P2Y12-inhibiting agents. However, the best anticoagulant, optimal agonist concentrations, increase in receptor number and sequence differences must be considered for any future studies.

Keywords: Anti-platelet studies; chacma baboon; platelet receptors

0 (Platelet Aggregation Inhibitors)
0 (Platelet Membrane Glycoproteins)
0 (Receptors, Cell Surface)
0 (Receptors, Purinergic P2)
1404-55-3 (Ristocetin)
27YG812J1I (Arachidonic Acid)
61D2G4IYVH (Adenosine Diphosphate)

Date Created: 20151113 Date Completed: 20170313 Latest Revision: 20170817

20221213

10.3109/09537104.2015.1095878

26559117