Yangambin: a new naturally-occurring platelet-activating factor receptor antagonist: binding and in vitro functional studies
1995
Castro-Faria-Neto, H.C. | Bozza, P.T. | Cruz, H.N. | Silva, C.L.M. | Violante, F.A. | Barbosa-Filho, J.M. | Thomas, G. | Martins, M.A. | Tibirica, E.V. | Noel, F. | Cordeiro, R.S.B. (FIOCRUZ, Rio de Janeiro (Brazil). Inst. Oswaldo Cruz. Dept. de Fisiologia e Farmacodinamica)
The effects of the furofuran lignan yangambin on rabbit platelet aggregation and binding of (3H)-PAF to rabbit platelet plasma membranes were studied. Log concentration-response curves to PAF were obtained in the presence or absence of increasing concentrations of yangambin. This lignan dose-dependently inhibited PAF-induced platelet aggregation in plateletrich plasma (PRP) and shifted PAF curves to the right without decreasing the maximal response. The Schild plot constructed from these data showed a slope of 1.17 and a pA2 of 6.45. Moreover, yangambin at 0.00001 M did not inhibit the platelet aggregation induced by ADP (0.5 micro M), collagen (O.1 microg/per ml), or thrombin (0.05 U/per ml). Biochemical studies showed that (3H)-PAF labelled in a saturable manner a single class of binding sites on platelet membranes with a Kd of 1.25 +- 0.24 nM and a maximal binding capacity (Bmax) of 14.9 +- 2.4 pmol/per mg protein. Both unlabelled PAF and yangambin competitively displaced (3H)-PAF binding with an IC50 of 1.54 +- 0.37 M and 1.93 +- 0.53 microM, respectively. The incubation of rabbit blood neutrophils with yangambin at 10 micro M did not prevent PAF-induced in vitro chemotaxis in conditions where the PAF antagonist SR 27417 at 10 micro M abolished the phenomenon. These results indicate that yangambin is an antagonist that selectively blocks PAF receptors on platelets.
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