Reantragoon S, Arrigo L M, Dweck H S, Rosenfeld L
Department of Pediatrics, New York Medical College, Valhalla, 10595, USA.
Arch Biochem Biophys. 1996 Mar 15;327(2):234-8. doi: 10.1006/abbi.1996.0115.
Heparin has been shown to lower the production/secretion of the vasoconstrictive peptide endothelin-1. Endothelin-1 production is stimulated by thrombin, and it has been proposed that heparin binds to the anion-binding exosite of thrombin, preventing it from stimulating endothelin-1 production. To further test this proposal, heparin was fractionated by strong anion exchange chromatography (QAE-Sephadex A-25) into four fractions. These fractions had anticoagulant activities that increased linearly with charge, as defined by the median salt concentration needed for elution from the column. The fractions also differed in the total number of sulfates per mole of heparin, which was dependent on the molecular mass of the fractions rather than charge density. The fractions were found to significantly differ fron each other in their ability to suppress endothelin-1 production. The fraction eluting from the ion exchange column at the highest salt concentration had the greatest suppressive effect. Addition of sodium or potassium chloride to the media interfered with the ET-1 suppressive effect of unfractionated heparin, whereas lithium chloride had no effect. These data show that charge interactions between heparin and thrombin may be important in regulating the production of endothelin-1 and in regulating other thrombin-dependent functions.
肝素已被证明可降低血管收缩肽内皮素 -1 的产生/分泌。内皮素 -1 的产生受凝血酶刺激，有人提出肝素与凝血酶的阴离子结合外位点结合，从而阻止其刺激内皮素 -1 的产生。为进一步验证这一说法，通过强阴离子交换色谱法（QAE - 葡聚糖 A - 25）将肝素分离成四个组分。这些组分具有抗凝活性，其活性随电荷呈线性增加，电荷由从柱上洗脱所需的中位盐浓度定义。各组分每摩尔肝素的硫酸盐总数也不同，这取决于组分的分子量而非电荷密度。结果发现，这些组分在抑制内皮素 -1 产生的能力上存在显著差异。在最高盐浓度下从离子交换柱洗脱的组分具有最大的抑制作用。向培养基中添加氯化钠或氯化钾会干扰未分级肝素对 ET -1 的抑制作用，而氯化锂则无此作用。这些数据表明，肝素与凝血酶之间的电荷相互作用可能在调节内皮素 -1 的产生以及调节其他凝血酶依赖性功能方面具有重要作用。
