Specific inhibition of PAF-acether-induced platelet activation by BN 52021 and comparison with the PAF-acether inhibitors kadsurenone and CV 3988.
BN 52021 is a chemically defined substance extracted from Ginkgo biloba leaves. Its inhibitory potency was tested on washed human platelets prepared so as to render them specifically sensitivity either to adenosine 5'-diphosphate (ADP), arachidonic acid (AA) or PAF-acether. Its activity and specificity were compared with those of two other reported inhibitors of PAF-acether effects: Kadsurenone and CV 3988. PAF-acether-induced aggregation of washed human platelets was concentration dependently inhibited by BN 52021 (IC50: 2.22 +/- 0.79 microM against 7.5 nM PAF-acether (n = 3)). Under the same experimental conditions the aggregation triggered by ADP was not modified and that induced by AA was marginally affected. The PAF-acether EC50 in platelet-rich plasma was increased 5- and 46-fold with 1 microM and 5 microM of BN 52021 respectively. This strongly suggested that the mechanism of action of BN 52021 is of the competitive type. Analysis of [3H]PAF-acether binding showed that BN 52021 as well as unlabelled PAF-acether prevented [3H]PAF-acether binding to intact washed platelets. In washed human platelets Kadsurenone affected only PAF-acether-induced aggregation (IC50: 0.8 +/- 0.4 microM (n = 3)), whereas CV 3988 inhibited the aggregation induced by ADP, AA and PAF-acether (IC50 were 10.2 +/- 2.3 microM; 2.2 +/- 0.1 microM; 1.0 +/- 0.1 microM respectively (n = 3). In contrast, up to 30 microM, CV 3988 was a specific antagonist of PAF-acether-induced platelet aggregation in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001572:Benzofurans; D001578:Benzopyrans / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004224:Diterpenes; D046934:Ginkgolides; D006801:Humans; D066298:In Vitro Techniques; D007783:Lactones; D017705:Lignans; D010742:Phospholipid Ethers; D010936:Plant Extracts / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology*
D001095:Arachidonic Acids; D001572:Benzofurans; D001578:Benzopyrans; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D017705:Lignans; D010742:Phospholipid Ethers; D010936:Plant Extracts; D010972:Platelet Activating Factor; D013844:Thiazoles; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; C037913:CV 3988; D000255:Adenosine Triphosphate; C044540:kadsurenone; C045856:ginkgolide B