Steinmeyer J, Kalbhen D A
Institut für Pharmakologie und Toxikologie, Universität Bonn, Fed. Rep. of Germany.
Arzneimittelforschung. 1991 Jan;41(1):77-80.
The in vitro effect of eglin C, glycosaminoglycan-peptide complex "DAK 16", glycosaminoglycan polysulfate and sodium pentosan polysulfate on the PMN-enzymes elastase and cathepsin G was investigated. The activity of elastase and cathepsin G was measured with the highly specific chromogenic substrates methoxysuccinyl-l-ala-l-ala-l-pro-l-val-p-nitroaniline and succinyl-l-ala-l-ala-l-pro-l-phenyl-alanin-p-nitroaniline. Eglin C and DAK 16 displayed a pronounced inhibition of PMN-elastase and PMN-cathepsin G. Surprisingly a higher amount of product in the elastase containing assays were found in the presence of glycosaminoglycan polysulfate and sodium pentosan polysulfate. The higher cleavage of the elastase substrate is related back to an electrostatic interaction of the polysulfates with this substrate. Both polysulfates strongly inhibited cathepsin G. The qualitatively and quantitatively different behavior of the drugs on elastase and cathepsin G are discussed with regard to their in vivo contribution to the therapy of chronic inflammatory joint diseases.
研究了依吉林C、糖胺聚糖 - 肽复合物“DAK 16”、糖胺聚糖多硫酸盐和戊聚糖多硫酸钠对中性粒细胞酶弹性蛋白酶和组织蛋白酶G的体外作用。用高特异性显色底物甲氧基琥珀酰 - L - 丙氨酸 - L - 丙氨酸 - L - 脯氨酸 - L - 缬氨酸 - 对硝基苯胺和琥珀酰 - L - 丙氨酸 - L - 丙氨酸 - L - 脯氨酸 - L - 苯丙氨酸 - 对硝基苯胺测量弹性蛋白酶和组织蛋白酶G的活性。依吉林C和DAK 16对中性粒细胞弹性蛋白酶和中性粒细胞组织蛋白酶G表现出明显的抑制作用。令人惊讶的是，在糖胺聚糖多硫酸盐和戊聚糖多硫酸钠存在的情况下，含弹性蛋白酶的测定中发现了更多的产物。弹性蛋白酶底物的更高裂解归因于多硫酸盐与该底物的静电相互作用。两种多硫酸盐都强烈抑制组织蛋白酶G。就这些药物在体内对慢性炎症性关节疾病治疗的贡献，讨论了它们对弹性蛋白酶和组织蛋白酶G在定性和定量上的不同行为。
