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Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  The P2Y1 Receptor Is Necessary for Adenosine 5-Diphosphate-Induced Platelet Aggregation Béatrice Hechler, Catherine Léon, Catherine Vial, Paul Vigne, Christian Frelin, Jean-Pierre Cazenave, and Christian Gachet From INSERM U.311, Etablissement de Transfusion Sanguine de Strasbourg, Strasbourg, Cédex, France; and Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, Valbonne, France. The human P2Y1 receptor heterologously expressed in Jurkat cells behaves as a specific adenosine 5-diphosphate (ADP) receptor at which purified adenosine triphosphate (ATP) is an ineffective agonist, but competitively antagonizes the action of ADP. This receptor is thus a good candidate to be the elusive platelet P2T receptor for ADP. In the present work, we examined the effects on ADP-induced platelet responses of two selective and competitive P2Y1 antagonists, adenosine-2-phosphate-5-phosphate (A2P5P) and adenosine-3-phosphate-5-phosphate (A3P5P). Results were compared with those for the native P2Y1 receptor expressed on the B10 clone of rat brain capillary endothelial cells (BCEC) and for the cloned human P2Y1 receptor expressed on Jurkat cells. A2P5P and A3P5P inhibited ADP-induced platelet shape change and aggregation (pA2 = 5) and competitively antagonized calcium movements in response to ADP in fura-2-loaded platelets, B10 cells, and P2Y1-Jurkat cells. In contrast, these compounds had no effect on ADP-induced inhibition of adenylyl cyclase in platelets or B10 cells, whereas known antagonists of platelet activation by ADP such as Sp-ATPS were effective. These identical signaling responses and pharmacologic properties suggest that platelets and BCEC share a common P2Y1 receptor involved in ADP-induced aggregation and vasodilation, respectively. This P2Y1 receptor coupled to the mobilization of intracellular calcium stores was found to be necessary to trigger ADP-induced platelet aggregation. The present results, together with data from the literature, also point to the existence of another as yet unidentified ADP receptor, coupled to adenylyl cyclase and responsible for completion of the aggregation response. Thus, the term, P2T, should no longer be used to designate a specific molecular entity. Blood, Vol. 92 No. 1 (July 1), 1998: pp. 152-159 © 1998 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Offermanns Activation of Platelet Function Through G Protein-Coupled Receptors Circ. 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