Effects of platelet activating factor antagonists on arachidonic acid-induced platelet aggregation and TXA2 formation.
The effects of the PAF receptor antagonists WEB 2086, WEB 2170, BN 50739 and BN 52021 on AA-induced platelet aggregation (PA) and TXA2 formation were investigated in comparison with the TXA2 synthetase inhibitor HOE 944 and the TXA2 receptor antagonist BM 13.177. All PAF antagonists tested were weak inhibitors of AA-induced PA and TXA2 formation (IC50 values between 80 and 2,737 mumol/l). HOE 944 was effective in concentrations 2-3 orders of magnitude lower than PAF antagonists in inhibiting TXA2 generation. These results imply that the inhibition of TXA2 formation is of minor relevance for the actions of the investigated PAF antagonists in AA-induced PA.
Heinroth-Hoffmann
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Martin Luther University Halle-Wittenberg, School of Medicine, Department of Pharmacology and Toxicology, GDR.
Hauser
A
A
Mest
H J
HJ
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004224:Diterpenes; D046934:Ginkgolides; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000187:drug effects; D017482:Receptors, Thromboxane; D013449:Sulfonamides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000097:blood*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014230:Triazoles / Q000494:pharmacology
D001095:Arachidonic Acids; D001381:Azepines; D004224:Diterpenes; D046934:Ginkgolides; D007093:Imidazoles; D007783:Lactones; D009281:Naphthalenes; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D014230:Triazoles; C052518:WEB 2086; C059526:6-(5-methylimidazol-1-yl)methyl-2-naphthoic acid hydrochloride; D016718:Arachidonic Acid; D013928:Thromboxane A2; C040624:sulotroban; C045856:ginkgolide B; D013930:Thromboxane-A Synthase