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 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.
Castro-Faria-Neto
H C
HC
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Bozza
P T
PT
Cruz
H N
HN
Silva
C L
CL
Violante
F A
FA
Barbosa-Filho
J M
JM
Thomas
G
G
Martins
M A
MA
Tibiriçá
E V
EV
Noel
F
F
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
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