INTERACTIONS IN-VITRO AND IN-VIVO BETWEEN PORCINE TISSUE KALLIKREIN AND PORCINE PLASMA PROTEINASE-INHIBITORS

被引:4
作者
BLACKBERG, M
OHLSSON, K
机构
[1] Department of Surgical Pathophysiology, University of Lund, Malmö General Hospital, S-214 01, Malmö
关键词
ALPHA-MACROGLOBULIN; ALPHA(1)-PROTEINASE INHIBITOR; BRADYKININ; TISSUE KALLIKREIN;
D O I
10.3109/00365519409087545
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The elimination of radio-iodinated porcine tissue kallikrein, after intravenous injection in the pig, showed a rapid initial clearance from plasma (T-1/2 approximately 10 min), followed by a phase of slower elimination (T-1/2 approximately 100 min). Gel filtration of plasma samples showed complexes with alpha(1)-alpha(2)-macroglobulin (A(1)a(2)-M) and alpha(1)-proteinase inhibitor (A(1)-PI), which decreased with time. The urinary excretion of undegraded tissue kallikrein was about 1.8%. Gel filtration of urine showed a minor peak representing free tissue kallikrein and a major peak representing degradation products. On average, 8.3% was found in the liver and 1.3% in the kidneys post mortem, indicating that these are the primary organs for the elimination of tissue kallikrein. The in vivo findings were supported by in vitro experiments. A(1)a(2)-M were found to be the major inhibitors of tissue kallikrein, when a mixture of the enzyme and porcine plasma was analysed by gel filtration, immunoelectrophoresis, crossed immunoelectrophoresis and autoradiography. A(1)-PI was only a minor inhibitor of tissue kallikrein. Both the A(1)a(2)-M and A(1)-PI complex formation was found to be time-dependent and slow; unbound glandular kallikrein was still detected after 12h, even when there was a molar surplus of A(1)a(2)-M and A(1)-PI. The complexes with A(1)a(2)-M and the unbound tissue kallikrein were found to be enzymatically active against low-molecular-weight chromogenic substrate. The total tissue kallikrein-inhibiting capacity of plasma seemed to be exceeded at a concentration of 800 KU/l when analysed using the rat uterus bioassay. A(1)a(2)-M appears to be the major inhibitor of tissue kallikrein in plasma and the complexes are removed mainly by the reticulo-endothelial system, such as that in the liver.
引用
收藏
页码:643 / 651
页数:9
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