title: Yangambin: a new naturally-occurring platelet-activating factor receptor antagonist: binding and in vitro functional studies.
abstract: 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 platelet-rich 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 10(-5) M did not inhibit the platelet aggregation induced by ADP (5 x 10(-7) M), collagen (0.1 microgram ml-1), or thrombin (0.05 U ml-1). 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 mg protein-1. Both unlabelled PAF and yangambin competitively displaced [3H]-PAF binding with an IC50 of 1.54 +/- 0.37 nM and 1.93 +/- 0.53 microM, respectively. The incubation of rabbit blood neutrophils with yangambin at 10(-5) M did not prevent PAF-induced in vitro chemotaxis in conditions where the PAF antagonist SR 27417 at 10(-5) M abolished the phenomenon. These results indicate that yangambin is an antagonist that selectively blocks PAF receptors on platelets.
authors.affiliation: Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: H C
authors.initials: HC
authors.lastname: Castro-Faria-Neto
authors.forename: P T
authors.initials: PT
authors.lastname: Bozza
authors.forename: H N
authors.initials: HN
authors.lastname: Cruz
authors.forename: C L
authors.initials: CL
authors.lastname: Silva
authors.forename: F A
authors.initials: FA
authors.lastname: Violante
authors.forename: J M
authors.initials: JM
authors.lastname: Barbosa-Filho
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: M A
authors.initials: MA
authors.lastname: Martins
authors.forename: E V
authors.initials: EV
authors.lastname: Tibiriçá
authors.forename: F
authors.initials: F
authors.lastname: Noel
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005663:Furans / Q000378:metabolism / Q000494:pharmacology*; D017705:Lignans / Q000378:metabolism / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010944:Plants / Q000737:chemistry*; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011817:Rabbits; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled
chemical_list: D005663:Furans; D017705:Lignans; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C082827:epiyangambin