EFFECT OF SR-27417 ON THE BINDING OF [H-3] PAF TO RABBIT AND HUMAN PLATELETS AND HUMAN POLYMORPHONUCLEAR LEUKOCYTES

SR 27417, the first member of a newly developed PAF antogonist series, fully and competitively displaced [H-3]PAF from its high-affinity binding sites on washed rabbit and human platelets with K(i) values of 57 +/- 0.02 and 50 +/- 0.8 pM (n = 3), respectively. Studies carried out in parallel demonstrated that SR 27417 was 5-7-times more potent than C-16-PAF itself and more than 50-60-fold as active as the best synthetic PAF antagonist yet described. Additionally, SR 27417 selectively and competitively inhibited the specific binding of [H-3]WEB-2086, a selective PAF receptor antagonist to its high-affinity receptors on washed rabbit platelets (IC50 = 0.18 +/- 0.01 nM). On human polymorphonuclear leukocytes, [H-3]PAF bound to two classes of specific binding sites with high (K(D) = 0.31 +/- 0.05 nM; B(max) = 1.2 +/- 0.07 fmol/10(6) cells) and low affinity (K(D) = 11.1 +/- 1.5 nM; B(max) = 13.7 +/- 0.8 fmol/10(6) cells). On these cells, SR 27417 selectively inhibited the specific binding of [H-3]PAF to its high- and low-affinity receptors (lC50 values of 0.17 +/- 0.02 and 6.9 +/- 0.7 nM, respectively) and displayed the same inhibitory pattern as that already reported on platelets. In conclusion, SR 27417 can be considered as the most potent PAF receptor antagonist described to date.