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[α-凝血酶对大鼠腹膜肥大细胞肝素分泌的刺激作用]

[Alpha-thrombin stimulation of heparin secretion by the peritoneal mast cells in rats].

作者信息

Umarova B A, Khlgatian S V, Strukova S M

出版信息

Biull Eksp Biol Med. 1989 Feb;107(2):131-3.

PMID:2466498
Abstract

The interaction of alpha-thrombin with connective tissue-type mast cells (CTMC) purified by Ficoll density gradient centrifugation has been examined. It was demonstrated that exposure of CTMC to polymixin (widely used histamine liberator) (3 mg/ml) induced the release of heparin and histamine. Exposure of CTMC to 10(-11) M alpha-thrombin resulted in increase of heparin secretion by 75.5% in relation to basal level. CTMC which were stimulated by very low concentrations of alpha-thrombin (10(-11)-10(-8) M) can release high level of heparin, but not histamine. We have a suggestion that the thrombin specificity is connected with the additional recognition binding site for high molecular substrates (HMS) distinct from the active centre. Unlike alpha-thrombin which has both the active centre and the recognition site for HMS, beta/gamma-thrombin with catalytic activity but with disrupted recognition site induced the heparin release from mast cells only at higher concentrations than alpha-thrombin. It was revealed that DIP-alpha-thrombin without proteolytic activity was unable to activate mast cells in contrast to alpha-thrombin. We consider that alpha-thrombin induced release of heparin by CTMC account for proteolytic and hormone-like activity enzyme by means of both the active centre and the additional recognition site for HMS.

摘要

研究了α-凝血酶与通过Ficoll密度梯度离心纯化的结缔组织型肥大细胞(CTMC)之间的相互作用。结果表明,将CTMC暴露于多粘菌素(广泛使用的组胺释放剂)(3mg/ml)会诱导肝素和组胺的释放。将CTMC暴露于10^(-11)M的α-凝血酶中,与基础水平相比,肝素分泌增加了75.5%。受到极低浓度α-凝血酶(10^(-11)-10^(-8)M)刺激的CTMC可以释放高水平的肝素,但不释放组胺。我们认为凝血酶的特异性与不同于活性中心的高分子底物(HMS)的额外识别结合位点有关。与具有活性中心和HMS识别位点的α-凝血酶不同,具有催化活性但识别位点被破坏的β/γ-凝血酶仅在比α-凝血酶更高的浓度下才诱导肥大细胞释放肝素。结果显示,与α-凝血酶相比,无蛋白水解活性的DIP-α-凝血酶无法激活肥大细胞。我们认为α-凝血酶诱导CTMC释放肝素是通过活性中心和HMS的额外识别位点实现的蛋白水解和类激素活性酶的作用。

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