Adenosine derived from ADP can contribute to inhibition of platelet aggregation in the presence of a P2Y12 antagonist.
OBJECTIVE
To investigate whether adenosine diphosphate (ADP)-derived adenosine might inhibit platelet aggregation, especially in the presence of a P2Y₁₂ antagonist, where the effects of ADP at the P2Y₁₂ receptor would be prevented.


RESULTS
Platelet aggregation was measured in response to thrombin receptor activator peptide by platelet counting in platelet-rich plasma (PRP) and whole blood in the presence of ADP and the P2Y₁₂ antagonists cangrelor, prasugrel active metabolite, and ticagrelor. In the presence of a P2Y₁₂ antagonist, preincubation of PRP with ADP inhibited aggregation; this effect was abolished by adenosine deaminase. No inhibition of aggregation occurred in whole blood except when dipyridamole was added to inhibit adenosine uptake into erythrocytes. The effects of ADP in PRP and whole blood were replicated using adenosine and were directly related to changes in cAMP (assessed by vasodilator-stimulated phosphoprotein phosphorylation). All results were the same irrespective of the P2Y₁₂ antagonist used.


CONCLUSIONS
ADP inhibits platelet aggregation in the presence of a P2Y₁₂ antagonist through conversion to adenosine. Inhibition occurs in PRP but not in whole blood except when adenosine uptake is inhibited. None of the P2Y₁₂ antagonists studied replicated the effects of dipyridamole in the experiments that were performed.
Cardiovascular Medicine, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom. david.iyu@nottingham.ac.uk
David
D
Iyú
Jackie R
JR
Glenn
Ann E
AE
White
Sue C
SC
Fox
Stan
S
Heptinstall
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology*; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects*; D018179:Receptors, Thrombin / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology; D000077486:Ticagrelor; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010879:Piperazines; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D018179:Receptors, Thrombin; D013876:Thiophenes; D000098662:Vasodilator-Stimulated Phosphoprotein; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; C117446:cangrelor; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine