Kaufmann R, Hoffmann J, Ramakrishnan V, Nowak G
Research Group Pharmacological Hemostaseology, Medical Faculty at the Friedrich-Schiller-Universität Jena, Germany.
Thromb Haemost. 1998 Dec;80(6):1018-21.
While effects of alpha-thrombin have been well characterized in different cell types, the biological function of intermediates of prothrombin activation is still undefined. Meizothrombin could be shown to be a potent agonist for vascular contraction which seems to be mediated by an interaction with the vascular smooth muscle. To explore this effect at intracellular signaling level, we used rat aortic smooth muscle cells and investigated the effect of the intermediates formed by cleavage of human prothrombin with ecarin, the prothrombin activator from Echis carinatus venom, on mobilization of free intracellular calcium. The ecarin-activated prothrombin induced very rapidly transient calcium mobilization in SMC's comparable to that observed with alpha-thrombin. We conclude that meizothrombin/meizothrombin desF1 (MT/MT desF1) are the most likely candidates for this effect. Furthermore, our results suggest the involvement of PAR-1-type thrombin receptors in MT/MT desF1-induced calcium signaling in rat aortic smooth muscle cells.
虽然α-凝血酶在不同细胞类型中的作用已得到充分表征，但凝血酶原激活中间体的生物学功能仍不明确。中凝血酶可被证明是血管收缩的有效激动剂，这似乎是通过与血管平滑肌的相互作用介导的。为了在细胞内信号传导水平上探索这种作用，我们使用大鼠主动脉平滑肌细胞，研究了由锯鳞蝰毒液中的凝血酶原激活剂依卡瑞林切割人凝血酶原形成的中间体对细胞内游离钙动员的影响。依卡瑞林激活的凝血酶原在平滑肌细胞中诱导非常快速的瞬时钙动员，与α-凝血酶观察到的情况相当。我们得出结论，中凝血酶/去F1中凝血酶（MT/MT desF1）最有可能是产生这种作用的候选物。此外，我们的结果表明PAR-1型凝血酶受体参与了MT/MT desF1诱导的大鼠主动脉平滑肌细胞钙信号传导。
