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Effect of clopidogrel treatment on ADP‐induced phosphorylations in rat platelets
Author(s) -
SAVI P.,
ARTÇANUTHURRY V.,
BORNIA J.,
GRELAC F.,
MACLOUF J.,
LEVYTOLEDANO S.,
HERBERT J. M.
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.d01-2132.x
Subject(s) - platelet , clopidogrel , phosphorylation , agonist , receptor , chemistry , adenosine diphosphate , tyrosine phosphorylation , stimulation , biophysics , biochemistry , pharmacology , medicine , endocrinology , biology , platelet aggregation , aspirin
Phosphorylations induced by 2‐MeS‐ADP, a potent agonist of platelet ADP receptors, have been studied in rat platelets, and the effect of clopidogrel, a compound which inhibits platelet aggregation by selectively reducing the binding of ADP to its low affinity receptors on platelets, has been determined. 2‐MeS‐ADP induced platelet activation (shape change and aggregation) simultaneously with the phosphorylation of myosin light chain (P 20 ) and plekstrin (P 47 ). Phosphorylation of P 20 and P 47 was transient, a maximum being observed 10 s after addition of the agonist when shape change reached its maximum. P 20 and P 47 phosphorylations were not strongly affected by clopidogrel treatment. Following stimulation of platelets with 2‐MeS‐ADP, several proteins were phosphorylated at tyrosine residues. Clopidogrel treatment inhibited the increase in phosphorylation of P 140 , P 100 , P 80/85 , P 66 and P 55 concomitantly with the inhibition of platelet aggregation. However, clopidogrel did not interfere with the early phosphorylation of the P 80/85 kD doublet which occurs at the time of the shape change. P 80/85 , identified by immunodetection as cortactin, could be involved in the reorganization of the cytoskeleton necessary for morphological changes. Thus, by using clopidogrel‐treated rat platelets, we were able to determine some of the phosphorylations coupled either to clopidogrel‐resistant high‐affinity ADP receptors leading to shape change or to clopidogrel sensitive low‐affinity ADP receptors coupled to the aggregation process.