YANGAMBIN - A NEW NATURALLY-OCCURRING PLATELET-ACTIVATING-FACTOR RECEPTOR ANTAGONIST - BINDING AND IN-VITRO FUNCTIONAL-STUDIES

The effects of the furofuran lignan yangambin on rabbit platelet aggre gation and binding of [H-3]-PAF to rabbit platelet plasma membranes we re studied. Log concentration-response curves to PAF were obtained in the presence or absence of increasing concentrations of yangambin. Thi s lignan dose-dependently inhibited PAF-induced platelet aggregation i n platelet-rich plasma (PRP) and shifted PAF curves to the right witho ut decreasing the maximal response. The Schild plot constructed from t hese data showed a slope of 1.17 and a pA(2) of 6.45. Moreover, yangam bin at 10(-5) M did not inhibit the platelet aggregation induced by AD P (5 x 10(-7) M), collagen (0.1 mu g ml(-1)), or thrombin (0.05 U ml(- 1)). Biochemical studies showed that [H-3]-PAF labelled in a saturable manner a single class of binding sites on platelet membranes with a K -d of 1.25 +/- 0.24 nM and a maximal binding capacity (B-max) of 14.9 +/- 2.4 pmol mg protein(-1). Both unlabelled PAF and yangambin competi tively; displaced [H-3]-PAF binding with an IC50 of 1.54 +/- 0.37 nM a nd 1.93 +/- 0.53 mu M, respectively. The incubation of rabbit blood ne utrophils with yangambin at 10(-5) M did not prevent PAF-induced in vi tro chemotaxis in conditions where the PAF antagonist SR 27417 at 10(- 5) M abolished the phenomenon. These results indicate that yangambin i s an antagonist that selectively blocks PAF receptors an platelets.