Effect of the PAF-receptor antagonist SM-12502 on human platelets.
We analyzed the effect of the PAF receptor antagonist (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) on human platelet aggregation as well as mediator release. After incubation of human platelet with different concentrations of SM-12502 the cells were subsequently stimulated with either the Ca ionophore A23187, with human thrombin, or with an activator of heterotrimeric G-proteins, sodium fluoride (NaF, in the presence of Al3+). Preincubation of platelets with the PAF receptor antagonist led to an inhibition of 12-lipoxygenase derived 12(S)-HETE and cyclooxygenase derived 12(S)-HHT. Pretreatment of platelets with the PAF receptor antagonist SM-12502 prior to activation with the Ca ionophore A23187 or PAF also inhibited platelet aggregation. Our data clearly indicate an inhibitory effect of the new PAF receptor antagonist SM-12502 on the formation of platelet derived inflammatory mediators of the lipoxygenase pathway as well as of the cyclooxygenase pathway, and furtherone, treatment with the PAF receptor antagonist diminished platelet aggregation after subsequent specific and unspecific activation.
Köller
M
M
Lehrstuhl für Medizinische Mikrobiologie und Immunologie, Ruhr-Universität Bochum, Germany.
Hilger
R A
RA
König
W
W
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000096:biosynthesis* / Q000235:genetics; D000535:Aluminum / Q000494:pharmacology; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis* / Q000235:genetics; D019204:GTP-Binding Proteins / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000502:physiology*; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction / Q000187:drug effects; D012969:Sodium Fluoride / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines; D013917:Thrombin / Q000494:pharmacology
D005231:Fatty Acids, Unsaturated; D007476:Ionophores; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013844:Thiazoles; D053778:Thiazolidines; C039351:platelet activating factor receptor; C065776:3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one; D000001:Calcimycin; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D012969:Sodium Fluoride; D000535:Aluminum; D001092:Arachidonate 12-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D013917:Thrombin; D019204:GTP-Binding Proteins; D002118:Calcium