Abstract
The aggregation of washed human platelets with paf-acether (paf) and [ 3H]paf binding were inhibited in a concentration- and time-dependent manner by three chemically defined ginkgolides (BN 52020, BN 52021, BN 52022) and their mixture, BN 52063 (molar ratio: 2 : 2 : 1). The IC 50 values for aggregation correlated well with the IC 50 values for [ 3H]paf binding (R-square 0.971). BN 52021, BN 52020, BN 52022 and BN 52063 (6 μM), as well as unlabelled paf (50 nM), displaced platelet-bound [ 3H]paf. Specific binding (total minus non-specific binding) in the presence of BN 52020 and BN 52063 was saturated but that observed in the presence of BN 52022 was not. However all ginkgolides shifted the dose-dependent paf-induced platelet aggregation curve rightwards. BN 52063 failed to modulate paf metabolism either in plasma or in the presence of platelets. The present results suggest that the ginkgolide mixture, BN 52063, acts at the paf binding level and the close correlation between ginkgolide effects on aggregation vs. paf binding illustrates the functional relevance of the putative paf platelet receptor.
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