Jaschonek K, Faul C, Daiss W, Weisenberger H
Prostaglandins Leukot Med. 1986 Oct;24(2-3):199-206. doi: 10.1016/0262-1746(86)90127-7.
Heparin is known to impair the antiaggregatory effectiveness of prostacyclin (PGI2) for adenosine diphosphate-induced aggregation in citrated platelet rich plasma. Thus porcine mucosal heparin (PMH) from different commercial sources was investigated for its ability to compete with specific platelet prostacyclin binding. In concentrations up to 250 IU/ml PMH itself did not interfere with the binding of 3 X 10(-9) M 9-3H-PGI2-sodium salt to intact washed platelets. The displacement of specifically bound PGI2 observed by PMH (Ki 60 IU/ml) containing 4-chloro-m-cresol (4-CC) was caused by the preservative (Ki 4-CC 3.0 X 10(-4) M). Although 60 IU/ml PMH (free of 4-CC) have been shown to inhibit basal 3 X 10(-5) M forskolin-, and 10(-8)M Iloprost-stimulated adenylate cyclase in platelet membranes (-63%, -62%, -83% respectively), no effect of PMH on 3H-cyclic-AMP formation has been observed when intact platelets were studied by 3H-adenine prelabeling technique. There is also no evidence that the preincubation of PGI2 (5 X 10(-7) M) with 1000 IU/ml PMH might neutralize the effectiveness of this eicosanoid. In contrast, PGI2 preincubated with PMH (10 min, 37 degrees C) caused a more pronounced increase of platelet 3H-cyclic AMP (+65%) compared with PGI2 incubated in 5 X 10(-2) M Tris-HCl, pH 7.4. Thus our data provide no evidence that PMH interferes with i) specific platelet PGI2 binding, ii) PGI2-stimulated cyclic AMP synthesis or iii) neutralizes PGI2 by formation of a biologically less active PGI2-PMH complex.
已知肝素会损害前列环素（PGI2）对枸橼酸化富血小板血浆中由二磷酸腺苷诱导的聚集的抗聚集效力。因此，对来自不同商业来源的猪黏膜肝素（PMH）与特异性血小板前列环素结合的竞争能力进行了研究。浓度高达250 IU/ml时，PMH本身并不干扰3×10⁻⁹ M 9-³H-PGI2钠盐与完整洗涤血小板的结合。含有4-氯间甲酚（4-CC）的PMH（Ki 60 IU/ml）观察到的特异性结合PGI2的置换是由防腐剂（Ki 4-CC 3.0×10⁻⁴ M）引起的。尽管已证明60 IU/ml PMH（不含4-CC）可抑制血小板膜中基础3×10⁻⁵ M福司可林、10⁻⁸ M伊洛前列素刺激的腺苷酸环化酶（分别为-63%、-62%、-83%），但在用³H-腺嘌呤预标记技术研究完整血小板时，未观察到PMH对³H-环磷酸腺苷形成的影响。也没有证据表明PGI2（5×10⁻⁷ M）与1000 IU/ml PMH预孵育可能会中和这种类花生酸的效力。相反，与在5×10⁻² M Tris-HCl，pH 7.4中孵育的PGI2相比，与PMH预孵育（10分钟，37℃）的PGI2导致血小板³H-环磷酸腺苷更明显的增加（+65%）。因此，我们的数据没有提供证据表明PMH会干扰：i）特异性血小板PGI2结合；ii）PGI2刺激的环磷酸腺苷合成；iii）通过形成生物活性较低的PGI2-PMH复合物来中和PGI2。
