Hwang S B, Cheah M J, Lee C S, Shen T Y
Thromb Res. 1984 Jun 15;34(6):519-31. doi: 10.1016/0049-3848(84)90256-1.
The inhibitory effects of several antiinflammatory agents on the specific binding of tritiated 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphorylcholine, (platelet activating factor, PAF), with its receptor on isolated rabbit platelet plasma membranes were investigated. Several potent cyclooxygenase inhibitors do not inhibit 3H-PAF binding to its receptor sites. Yet, three others, indomethacin, phenylbutazone and sulfinpyrazone, as well as three non-cyclooxygenase inhibitors, the 3',4'-dimethoxy analog of indomethacin, the prodrug sulindac and its sulfone metabolite, are moderately active at relatively high concentrations (50 - 100 microM). Parallel inhibitions of 3H-PAF binding and PAF-induced platelet aggregation by derivatives of these antiinflammatory agents suggest that these inhibitors are probably interacting with the functional binding sites of PAF. The results clearly indicate that the configuration of PAF binding site is very different from the inhibitory site of cyclooxygenase. A preference for oxygenated substituents in these hydrophobic molecules to inhibit the PAF-receptor binding is noted. Some binding characteristics of the receptor are briefly discussed.
研究了几种抗炎药对氚标记的1-O-烷基-2-O-乙酰基-sn-甘油-3-磷酸胆碱（血小板活化因子，PAF）与其在离体兔血小板质膜上的受体特异性结合的抑制作用。几种强效环氧化酶抑制剂不抑制3H-PAF与其受体位点的结合。然而，另外三种药物，即吲哚美辛、保泰松和磺吡酮，以及三种非环氧化酶抑制剂，吲哚美辛的3'，4'-二甲氧基类似物、前药舒林酸及其砜代谢物，在相对较高浓度（50 - 100 microM）时具有中等活性。这些抗炎药衍生物对3H-PAF结合和PAF诱导的血小板聚集的平行抑制表明，这些抑制剂可能与PAF的功能性结合位点相互作用。结果清楚地表明，PAF结合位点的结构与环氧化酶的抑制位点非常不同。注意到这些疏水分子中含氧取代基对抑制PAF-受体结合的偏好。简要讨论了该受体的一些结合特性。
