Differential involvement of the P2Y1 and P2YT receptors in the morphological changes of platelet aggregation.
The relative contributions of the P2Y1 and P2YT receptors to the morphological changes induced in platelets by ADP or ADP-releasing agonists were assessed using two P2 antagonists, A2P5P and AR-C67085, selective for P2Y1 and P2YT, respectively. The P2Y1 receptor was found to be involved in i) the centralization of secretory granules elicited by ADP, ii) the formation of filopodia induced by released ADP in weakly activated platelets and iii) actin polymerization and the cytoskeletal translocation of cdc42, rac1 and rhoA, in an integrin alphaIIbbeta3 dependent manner, in ADP-stimulated platelets. In contrast, the P2YT receptor was shown i) to be essential for the formation of stable macroaggregates, ii) to enhance actin polymerization and the cytoskeletal translocation of small GTPases, probably through amplification of platelet aggregation, and iii) not to be involved in the early steps of platelet activation since its blockade did not affect the cytoskeletal translocation of rhoA.
Eckly
A
A
INSERM U.311, Etablissement Français du Sang-Alsace, Strasbourg, France.
Gendrault
J L
JL
Hechler
B
B
Cazenave
J P
JP
Gachet
C
C
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000199:Actins / Q000032:analysis; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000648:ultrastructure*; D020013:Calcium Signaling / Q000187:drug effects; D048429:Cell Size; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D008854:Microscopy, Electron; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D013917:Thrombin / Q000494:pharmacology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
C117445:AR C67085MX; D000199:Actins; D008565:Membrane Proteins; C546382:P2RY1 protein, human; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; C020857:phosphoadenosine diphosphoribose; D000246:Adenosine Diphosphate Ribose; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D013917:Thrombin; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein