Selective inhibition of adrenaline‐induced human platelet aggregation by the structurally related Paf antagonist Ro 19–3704

1 Two non‐lipid antagonists of platelet‐activating factor acether (Paf), BN 52021 and WEB 2086, at concentrations which completely blocked Paf‐induced platelet aggregation, failed to interfere with aggregation by adrenaline. In contrast, Ro 19–3704, a structurally related antagonist of Paf, inhibited concentration‐dependently aggregation induced by adrenaline or by the simultaneous addition of submaximal concentrations of adrenaline and Paf. Reversal of aggregation was obtained when Ro 19–3704 was added to the platelet suspension after adrenaline. 2 Ro 19–3704 was selective for Paf and adrenaline since it failed to interfere with platelet aggregation induced by arachidonic acid or ADP. CV‐3988, an antagonist of Paf structurally similar to Ro 19–3704, also inhibited adrenaline‐induced aggregation. However, a morpholine analogue (MA) of Paf, which has no anti‐Paf activity, failed to interfere with the aggregation induced by adrenaline. This suggests that the effect of Ro 19–3704 and CV‐3988 on adrenaline is not simply due to their lipid structure. 3 Experiments on plasma membrane preparations showed that Ro 19–3704 inhibited [ 3 H]‐yohimbine binding with an inhibition constant ( K i ) of 7 ± 3 μ m . In contrast, BN 52021 and MA did not interfere with [ 3 H]‐yohimbine binding. Equilibrium binding experiments showed that Ro 19–3704 increased the apparent K D of [ 3 H]‐yohimbine binding from 2.02 ± 0.15 to 7.3 ± 0.4 n m . The Paf antagonist Ro 19–3704 interacts specifically with the α 2 ‐adrenoceptor and may thus prevent the early steps involved in the mechanism of adrenaline‐induced platelet activation.