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Role of P2Y1 purinoceptor in ADP‐induced platelet activation
Author(s) -
Savi P,
Beauverger P,
Labouret C,
Delfaud M,
Salel V,
Kaghad M,
Herbert J.M
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00025-8
Subject(s) - platelet activation , platelet , chemistry , adenosine diphosphate , biophysics , microbiology and biotechnology , biochemistry , pharmacology , platelet aggregation , immunology , medicine , biology
ADP acts as an agonist of platelet aggregation via specific receptors which are still to be characterised. Amplification by PCR of a human platelet cDNA library confirmed the presence of mRNA of the P2Y1 receptor in platelets. In order to determine if these P2Y1 receptors were involved in ADP‐induced platelet activation, we determined the effects of A3P5PS, an antagonist of the P2Y1 receptor, on the binding of [ 33 P]2‐MeS‐ADP, a potent analogue of ADP. We found that A3P5PS displaced about 27% of [ 33 P]2‐MeS‐ADP binding, a receptor population which has been shown to be resistant to treatment with clopidogrel, a selective anti‐ADP agent. A3P5PS specifically inhibited 2‐MeS‐ADP‐induced shape change and calcium increase but did not affect adenylyl cyclase down‐regulation. 2‐MeS‐ADP‐induced platelet aggregation was also inhibited by A3P5PS but was restored when platelets were further activated by serotonin, a non‐aggregating compound, therefore suggesting that P2Y1‐mediated stimulation is an absolute prerequisite for ADP to induce platelet aggregation and a key event for platelet activation and aggregation to occur. These results therefore show that ADP‐induced aggregation cannot be attributed to activation of P2Y1 alone, but must be attributed to the simultaneous activation of the high affinity receptor (P2Y1) and a low affinity receptor of ADP (still to be discovered), each of them essential, but neither able to trigger aggregation alone.