Antagonists of PAF-acether do not suppress thrombin-induced aggregation of ADP-deprived and aspirin-treated human platelets.
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 compounds 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 antagonists 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.
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003435:Crotalid Venoms / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004224:Diterpenes; D046934:Ginkgolides; D005995:Glyceryl Ethers; D006801:Humans; D007783:Lactones; D037181:Lectins, C-Type; D010742:Phospholipid Ethers; D010936:Plant Extracts / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors*
D003435:Crotalid Venoms; D016861:Cyclooxygenase Inhibitors; D004224:Diterpenes; D046934:Ginkgolides; D005995:Glyceryl Ethers; D007783:Lactones; D037181:Lectins, C-Type; D010742:Phospholipid Ethers; D010936:Plant Extracts; D010972:Platelet Activating Factor; D011725:Pyridines; D013844:Thiazoles; C053235:Ro 19-3704; C028890:convulxin; D000244:Adenosine Diphosphate; C037913:CV 3988; D000255:Adenosine Triphosphate; C052520:3-(3-pyridinyl)-1H,3H-pyrrolo(1,2-c)thiazole-7-carboxamide; C045856:ginkgolide B; D013917:Thrombin; D001241:Aspirin