ADP receptor antagonists inhibit platelet aggregation induced by the chemokines SDF-1, MDC and TARC.
The ability of the chemokines SDF-1, MDC and TARC to induce platelet aggregation depends strongly on low levels of ADP. The ADP receptors involved have now been characterized using the P2Y(1) and P2T(AC) receptor antagonists, A2P5P and AR-C69931MX. Stimulation of aggregation by the chemokines at 10 s was not blocked by AR-C69931MX, but was strongly inhibited by A2P5P. Pertussis toxin abolished the chemokine-stimulated aggregation. We conclude that the P2Y(1) ADP receptor plays a critical role in the initial phases of SDF-1-, MDC- and TARC-induced platelet aggregation, which involve a pertussis toxin-sensitive G protein.
Suttitanamongkol
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Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA. ss2fn@virginia.edu
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D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D037342:Pertussis Toxin; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
C106230:CCL17 protein, human; C515482:CCL22 protein, human; C515255:CXCL12 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D010566:Virulence Factors, Bordetella; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; C117446:cangrelor; D037342:Pertussis Toxin; D013917:Thrombin; D019204:GTP-Binding Proteins