PHARMACOLOGICAL EVIDENCE FOR THE PUTATIVE EXISTENCE OF 2 DIFFERENT SUBTYPES OF PAF RECEPTORS ON PLATELETS AND LEUKOCYTES - STUDIES WITH YANGAMBIN

Yangambin, a new naturally-occuring platelet activating receptor (PAF) receptor antagonist competitively displaced [H-3]-PAF from its high a ffinity binding sites on washed human platelets with a Ki value of 1.1 +/- 0.3 mu M (n = 3). Studies carried out in parallel demonstrated th at SR 27417, a newly-developed PAF receptor antagonist also antagonize d [H-3]-PAF binding to these cells with a Ki value of 51 +/- 2 pM. SR 27417 (N-(2-dimethylamino ethyl)-N-(3-pyridinyl methyl) [4-(2,4,6-trii sopropyl phenyl) thiazol-2-yl] amine) selectively and competitively in hibited the specific binding of [H-3]-PAF on human polymorphonuclear l eukocytes (Ki = 65 +/- 5.2 pM) whereas high doses of yangambin remaine d ineffective. Yangambin inhibited PAF-induced aggregation of human pl atelets in vitro (IC50 = 1.0 +/- 0.2 mu M) but had no effect PAF-induc ed oxidative burst in human polymorphonuclear leukocytes. In guinea pi gs, yangambin inhibited PAF-induced thrombocytopenia but did not affec t leukocytopenia whereas SR 27417 afforded complete protection against both PAF-induced thrombocytopenia and leukocytopenia. In conclusion, yangambin discriminates between two different types of PAF receptors o n platelets and polymorphonuclear leukocytes and can be considered as the first PAF receptor antagonist described to date exhibiting such an effect. (C) 1997 Elsevier Science B.V.