Fortini A, Modesti P A, Abbate R, Gensini G F, Neri Serneri G G
Thromb Res. 1985 Nov 1;40(3):319-28. doi: 10.1016/0049-3848(85)90267-1.
Heparin has been reported to antagonize the platelet antiaggregating activity of prostacyclin (PGI2) and prostaglandin D2 (PGD2). To investigate whether heparin interferes with PGI2 and/or PGD2 binding to the specific membrane platelet receptors, the number and the affinity of binding sites for tritiated PGI2 and PGD2 were determined in 8 healthy subjects (aged 25-32; 4 for PGI2 and 4 for PGD2 studies) in the absence and in the presence of heparin. Preliminary aggregation tests indicated that the heparin concentration tested (2 I.U./ml) reduced the antiaggregating activity of PGI2 and PGD2. Heparin, when preincubated with platelet suspension, did not induce any significant change in the number/platelet (bs/plt) and affinity (Kd) of PGI2 and PGD2 binding sites (bs) in comparison to control values (PGI2 high affinity bs: bs/plt = 106 +/- 12 vs 107 +/- 17 - Kd = 9.7 +/- 3.1 vs 10.0 +/- 2.3 nM; PGI2 low affinity bs: bs/plt = 3551 +/- 233 vs 3670 +/- 465 - Kd = 877 +/- 125 +/- 125 vs 833 +/- 104 nM; PGD2 bs: bs/plt = 228 +/- 14 vs 234 +/- 24 - Kd = 68 +/- 10 vs 73 +/- 7 nM; p greater than 0.4 for all the differences). No significant binding modification was also observed when heparin was preincubated with 3H-PGI2 and 3H-PGD2. The present demonstration that heparin does not interfere with PGI2 and PGD2 binding to platelets is consistent with the hypothesis that heparin reduces the antiaggregating effects of PGI2 and PGD2 by directly potentiating platelet aggregation.
据报道，肝素可拮抗前列环素（PGI2）和前列腺素D2（PGD2）的血小板抗聚集活性。为研究肝素是否干扰PGI2和/或PGD2与血小板特异性膜受体的结合，在8名健康受试者（年龄25 - 32岁；4名用于PGI2研究，4名用于PGD2研究）中，测定了在不存在和存在肝素的情况下，氚标记的PGI2和PGD2结合位点的数量和亲和力。初步聚集试验表明，所测试的肝素浓度（2国际单位/毫升）降低了PGI2和PGD2的抗聚集活性。与对照值相比，当肝素与血小板悬液预孵育时，PGI2和PGD2结合位点的数量/血小板（bs/plt）和亲和力（Kd）没有发生任何显著变化（PGI2高亲和力结合位点：bs/plt = 106 ± 12对107 ± 17 - Kd = 9.7 ± 3.1对10.0 ± 2.3纳摩尔；PGI2低亲和力结合位点：bs/plt = 3551 ± 233对3670 ± 465 - Kd = 877 ± 125对833 ± 104纳摩尔；PGD2结合位点：bs/plt = 228 ± 14对234 ± 24 - Kd = 68 ± 10对73 ± 7纳摩尔；所有差异的p均大于0.4）。当肝素与3H - PGI2和3H - PGD2预孵育时，也未观察到显著的结合修饰。目前关于肝素不干扰PGI2和PGD2与血小板结合的证明与以下假设一致，即肝素通过直接增强血小板聚集来降低PGI2和PGD2的抗聚集作用。
