Okamoto S, Okamoto U, Wanaka K, Hijikata-Okunomiya A, Bohgaki M, Naito T, Horie N, Okada Y
Kobe Research Projects on Thrombosis and Haemostasis, Saiseikai-Hospital, Japan.
Adv Exp Med Biol. 1989;247B:29-34. doi: 10.1007/978-1-4615-9546-5_5.
The synthetic inhibitors of plasma kallikrein (PK) were found, which are called PKSI-1007, PKSI-0180 and PKSI-0527 in our laboratories. (1) The inhibitors inhibited PK competitively with D-Pro-Phe-Arg-pNA and the Ki values obtained were considerably small, 10(-6) M-10(-7) M. However, the Ki values for glandular kallikrein (GK), plasmin (PL), thrombin (TH) and factor Xa (FXa) were larger. In particular, a selectivity of PKSI-0527 towards PK was very high and the toxicity was weak (i.v. LD50 for mice is over 100 mg/kg). (2) The inhibitors were effective (a) to prevent the bradykinin formation in the kaolin-activated human plasma and the acid-treated ascites taken from the mice bearing Sarcoma 180, (b) to prolong the coagulation time by contact activation, and (c) to inhibit the enhancement of ADP-platelet aggregation by PK. The results indicated that the some PKSI-inhibitors will be much useful for the basic studies, furthermore they deem to be even promising towards the clinical application.
我们在实验室中发现了血浆激肽释放酶（PK）的合成抑制剂，分别命名为PKSI - 1007、PKSI - 0180和PKSI - 0527。（1）这些抑制剂与D - Pro - Phe - Arg - pNA竞争性抑制PK，所得Ki值相当小，为10^(-6) M - 10^(-7) M。然而，它们对腺体激肽释放酶（GK）、纤溶酶（PL）、凝血酶（TH）和因子Xa（FXa）的Ki值较大。特别是，PKSI - 0527对PK的选择性非常高，且毒性较弱（小鼠静脉注射LD50超过100 mg/kg）。（2）这些抑制剂具有以下作用：（a）可防止高岭土激活的人血浆和取自荷肉瘤180小鼠的酸处理腹水生成缓激肽；（b）通过接触激活延长凝血时间；（c）抑制PK对ADP诱导的血小板聚集的增强作用。结果表明，某些PKSI抑制剂对基础研究非常有用，而且它们在临床应用方面似乎也很有前景。
