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, Volume 21, Issue 1–2, pp 195–202 | Cite as

Antagonists of PAF-acether do not suppress thrombin-induced aggregation of ADP-deprived and aspirin-treated human platelets

  • S. Adnot
  • D. Joseph
  • B. B. Vargaftig
Platelets and Thrombosis

Abstract

Four chemically distinct PAF-acether antagonists were used to test the hypothesis that the cyclooxygenase and ADP-independent thrombin-induced aggregation of human platelets is due to PAF-acether. The compouds 48740 RP, CV-3988, BN 52021 and Ro 19-3704 inhibited aggregation by PAF-acether whereas 48740 RP also interfered with aggregation by arachidonic acid, U 46619, collagen and thrombin. Aspirin-treated platelets aggregated in response to PAF-acether and to 0.25 U/ml thrombin as much as control platelets in absence of detectable thromboxane A2, and were less responsive to 0.05–0.1 U/ml. Thrombin-induced aggregation of aspirin-treated platelets was unaffected by the PAF-acether antagnists BN 52021, CV-3988 and Ro 19-3704. In separate experiments, platelets were exposed for five min to convulxin, a glycoprotein extracted from a snake venom which depletes granular ADP and ATP. A combination of PGI2, aspirin and anticrotalid serum used to disaggregate allowed the recovery of approximately 80% free platelets, which failed to respond to PAF-acether but still aggregated in presence of thrombin. This residual ADP and cyclooxygenase-independent aggregation is not accountable for by the platelet formation of PAF-acether, since it was not modified by the latters' antagonists nor by platelet exposure to convulxin. Our results do not support the proposal that PAF-acether mediates a third pathway of human platelet aggregation.

Keywords

Collagen Aspirin Arachidonic Acid Thrombin Platelet Aggregation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag 1987

Authors and Affiliations

  • S. Adnot
    • 1
  • D. Joseph
    • 1
  • B. B. Vargaftig
    • 1
  1. 1.Untté des Venins-Unité Associée Institut Pasteur/INSERM n° 285 Department de Physiopathologie expérimentale Institut PasteurParisFrance

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