Fossum S, Hoem N O, Johannesen S, Korpberget M, Nylund E, Sandem S, Briseid K
Department of Pharmacology, University of Oslo, Norway.
Thromb Res. 1994 Jun 1;74(5):477-85. doi: 10.1016/0049-3848(94)90268-2.
The plasma levels of contact activation factors were measured in women using a low estrogen dose oral contraceptive (OC). Basic values for factor XII (FXII), factor XI (FXI), prekallikrein (PK), and high molecular weight kininogen (HK) were obtained in immunoassays by comparing with control plasma. The plasma levels of FXII and PK were significantly increased in OC plasma, to 147% and 146% respectively, whereas no significant increase could be registered for FXI (106%) or for HK (107%). Functional assays carried out with different peptide substrates (S-2222 for FXIIa, and S-2222, S-2302 and Bz-Pro-Phe-Arg-pNA for kallikrein) showed increases in OC plasma to about 150% for both proteases, in accordance with results obtained in radial immunodiffusion (RID). However, when FXIIa was measured with the high molecular weight substrate PK, no significant increase could be registered. Further experiments suggested this result to be due to the low level of FXI present in OC plasma, as compared to the levels of FXII and PK. Assays were carried out in mixtures of test plasma (OC or control plasma) and plasma deficient in FXI or FXII. The results obtained suggested that FXIa was present in some kind of association with part of FXIIa and part of kallikrein present. At low concentrations of FXI the functional activity of FXIIa was reduced, and the assay data indicated that an appropriate level of FXI was required to obtain maximum rate of hydrolysis of prekallikrein by FXIIa.(ABSTRACT TRUNCATED AT 250 WORDS)
对使用低剂量雌激素口服避孕药(OC)的女性进行了接触激活因子的血浆水平测定。通过与对照血浆比较,在免疫测定中获得了因子 XII(FXII)、因子 XI(FXI)、前激肽释放酶(PK)和高分子量激肽原(HK)的基础值。OC 血浆中 FXII 和 PK 的血浆水平显著升高,分别达到 147%和 146%,而 FXI(106%)或 HK(107%)未出现显著升高。用不同肽底物(用于 FXIIa 的 S-2222,以及用于激肽释放酶的 S-2222、S-2302 和 Bz-Pro-Phe-Arg-pNA)进行的功能测定显示,两种蛋白酶在 OC 血浆中的活性均增加至约 150%,这与径向免疫扩散(RID)获得的结果一致。然而,当用高分子量底物 PK 测量 FXIIa 时,未出现显著升高。进一步的实验表明,该结果是由于与 FXII 和 PK 的水平相比,OC 血浆中 FXI 的水平较低。在测试血浆(OC 或对照血浆)与缺乏 FXI 或 FXII 的血浆混合物中进行了测定。获得的结果表明,FXIa 与部分存在的 FXIIa 和部分激肽释放酶以某种形式结合。在低浓度的 FXI 时,FXIIa 的功能活性降低,测定数据表明需要适当水平的 FXI 才能使 FXIIa 对前激肽释放酶的水解速率达到最大值。(摘要截断于 250 字)