Schmaier A H, Wahl R, Fisher S J, Brenner D
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0640, USA.
Thromb Res. 1998 Dec 15;92(6):293-7. doi: 10.1016/s0049-3848(98)00142-x.
Recent evidence has shown that plasma high molecular weight kininogen and both kininogens have the ability to modulate prekallikrein activation and thrombin-induced platelet activation, respectively. However, nothing is known about the plasma clearance and tissue distribution of these proteins. We examined the in vivo pharmacokinetics of high (HK) and low (LK) molecular weight kininogens in rats. 125I-HK and -LK molecular weight kininogens' clearance in rats best-fitted a biexponential model. For HK, the t1/2alpha and t1/2beta were 0.6 and 9.5 h and for LK, 0.78 and 7.4 h, respectively. 125I-kinin-free HK (cleaved HK) was cleared with a t1/2alpha and t1/2beta of 0.45 and 9.9 h, respectively. 125I-Domain 3 of kininogens was cleared with a t1/2beta and t1/2c of 0.99 and 13.3 h, respectively. HK was mostly concentrated in lung; LK, domain 3, and cleaved HK were mostly concentrated in kidney. The kininogens were also concentrated in liver, spleen, and skin. These studies indicate that protein size rather than form is the major determinant of its clearance. Furthermore, the distribution of the kininogens is where bradykinin metabolism and activity are well described.
最近有证据表明，血浆高分子量激肽原和两种激肽原分别具有调节前激肽释放酶激活和凝血酶诱导的血小板激活的能力。然而，关于这些蛋白质的血浆清除率和组织分布却一无所知。我们研究了大鼠体内高分子量（HK）和低分子量（LK）激肽原的药代动力学。125I-HK和-LK分子量激肽原在大鼠体内的清除率最符合双指数模型。对于HK，t1/2α和t1/2β分别为0.6和9.5小时，对于LK，分别为0.78和7.4小时。无激肽的125I-HK（裂解HK）的清除率t1/2α和t1/2β分别为0.45和9.9小时。激肽原的125I-结构域3的清除率t1/2β和t1/2c分别为0.99和13.3小时。HK主要集中在肺中；LK、结构域3和裂解HK主要集中在肾中。激肽原也集中在肝脏、脾脏和皮肤中。这些研究表明，蛋白质大小而非形式是其清除率的主要决定因素。此外，激肽原的分布与缓激肽代谢和活性得到充分描述的部位一致。
