Herbert J M, Lamarche I, Dol F
Sanofi Recherche, Haemobiology Research Department, Toulouse, France.
FEBS Lett. 1992 Apr 20;301(2):155-8. doi: 10.1016/0014-5793(92)81237-g.
The synthetic peptide, SFLLRNPNDKYEPF, has been recently described as a peptide mimicking the new amino-terminus created by cleavage of the thrombin receptor, therefore acting as an agonist of the thrombin receptor. This peptide was a potent mitogen for rabbit arterial smooth muscle cells (SMC) and exhibited the same activity as that of native alpha-thrombin. Both compounds stimulated the proliferation of growth-arrested SMCs with half-maximum mitogenic responses at 1 nM. NAPAP, a synthetic inhibitor of the enzymatic activity of thrombin, specifically inhibited thrombin-induced SMC growth (IC50 = 0.35 +/- 0.04 microM) but was without effect on the mitogenic effect of the agonist peptide. These results therefore demonstrate that the mitogenic effect of alpha-thrombin for SMCs is intimately linked to its esterolytic activity. Heparin, which inhibited fetal calf serum-induced SMC growth, was without effect on thrombin-induced SMC growth but strongly reduced the mitogenic effect of the agonist peptide (IC50 = 32 +/- 5 micrograms/ml). This effect was not related to the anti-coagulant activity of heparin but was highly dependent on molecular mass and on the global charge of the molecule and was also observed for other sulphated polysaccharides such as pentosan polysulphate.
合成肽SFLLRNPNDKYEPF最近被描述为一种模拟凝血酶受体裂解后产生的新氨基末端的肽，因此可作为凝血酶受体的激动剂。该肽是兔动脉平滑肌细胞（SMC）的一种强效促有丝分裂原，其活性与天然α-凝血酶相同。两种化合物均能刺激生长停滞的SMC增殖，在1 nM时产生半数最大促有丝分裂反应。NAPAP是一种凝血酶酶活性的合成抑制剂，能特异性抑制凝血酶诱导的SMC生长（IC50 = 0.35 +/- 0.04 microM），但对激动剂肽的促有丝分裂作用无影响。因此，这些结果表明α-凝血酶对SMC的促有丝分裂作用与其酯解活性密切相关。肝素可抑制胎牛血清诱导的SMC生长，但对凝血酶诱导的SMC生长无影响，但能强烈降低激动剂肽的促有丝分裂作用（IC50 = 32 +/- 5微克/毫升）。这种作用与肝素的抗凝活性无关，但高度依赖于分子质量和分子的整体电荷，其他硫酸化多糖如戊聚糖多硫酸盐也有此现象。
