Effect of BN 52021, a specific antagonist of platelet activating factor (PAF-acether), on calcium movements and phosphatidic acid production induced by PAF-acether in human platelets.
32P-labelled human platelets loaded with quin 2 and pretreated with aspirin were stimulated with 1-100 nM platelet activating factor (PAF-acether or 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in a medium containing the ADP-scavenging system creatine phosphate/creatine phosphokinase. Under these conditions, PAF-acether evoked a characteristic fluorescence change allowing to quantify elevations in cytoplasmic free Ca2+ from internal stores (Ca2+ mobilization) or from external medium (Ca2+ influx), as well as an increased production of phosphatidic acid, reflecting phospholipase C activation. These effects, which can be attributed to PAF-acether only and not to released products such as ADP or thromboxane A2, were strongly inhibited in a dose-dependent manner by BN 52021, a specific antagonist of PAF-acether isolated from Ginkgo biloba. As the drug remained inactive against the same effects elicited by thrombin, it is concluded that BN 52021 does not interfere directly with the mechanism of transmembrane signalling involving inositol-phospholipids or (and) some putative receptor-operated channels, but rather acts on the binding of PAF-acether to its presumed membrane receptor.
D000634:Aminoquinolines; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D046934:Ginkgolides; D006801:Humans; D007783:Lactones; D010712:Phosphatidic Acids / Q000096:biosynthesis*; D010761:Phosphorus Radioisotopes; D010936:Plant Extracts / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010738:Type C Phospholipases / Q000502:physiology
D000634:Aminoquinolines; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010712:Phosphatidic Acids; D010761:Phosphorus Radioisotopes; D010936:Plant Extracts; D010972:Platelet Activating Factor; C045856:ginkgolide B; D010738:Type C Phospholipases; C035739:Quin2; D002118:Calcium