Castro-Faria-Neto H C, Bozza P T, Cruz H N, Silva C L, Violante F A, Barbosa-Filho J M, Thomas G, Martins M A, Tibiriçá E V, Noel F
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Planta Med. 1995 Apr;61(2):101-5. doi: 10.1055/s-2006-958025.
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.
研究了呋喃呋喃木脂素洋橄榄苦苷对兔血小板聚集以及[3H]-血小板活化因子（PAF）与兔血小板质膜结合的影响。在存在或不存在浓度递增的洋橄榄苦苷的情况下，获得了对PAF的对数浓度-反应曲线。这种木脂素剂量依赖性地抑制富含血小板血浆（PRP）中PAF诱导的血小板聚集，并使PAF曲线右移，而不降低最大反应。根据这些数据构建的Schild图显示斜率为1.17，pA2为6.45。此外，10^(-5) M的洋橄榄苦苷不抑制由ADP（5×10^(-7) M）、胶原（0.1微克/毫升）或凝血酶（0.05单位/毫升）诱导的血小板聚集。生化研究表明，[3H]-PAF以可饱和的方式标记血小板膜上的一类单一结合位点，解离常数（Kd）为1.25±0.24 nM，最大结合容量（Bmax）为14.9±2.4 pmol/mg蛋白^(-1)。未标记的PAF和洋橄榄苦苷都竞争性地取代[3H]-PAF的结合，IC50分别为1.54±0.37 nM和1.93±0.53 microM。在10^(-5) M的PAF拮抗剂SR 27417消除该现象的条件下，用10^(-5) M的洋橄榄苦苷孵育兔血中性粒细胞并不能阻止PAF诱导的体外趋化性。这些结果表明洋橄榄苦苷是一种选择性阻断血小板上PAF受体的拮抗剂。
