Morris B J, Lawrence C H
Biochim Biophys Acta. 1980 Mar 14;612(1):137-42. doi: 10.1016/0005-2744(80)90286-7.
Puff adder venom, which has been pretreated with phenylmethylsulphonyl fluoride and extensively dialysed, is capable of destroying selectively proteinase inhibitory activity in human plasma by an action of an EDTA-sensitive venom proteinase. We found that incubation of 1/5 vol. of such venom with human plasma at 25 degrees C leads to a concomitant increase in renin to 4.4 times control by 5 h. The activation of inactive renin was abolished by 10 mM EDTA and the rate of activation was reduced by 50% in the presence of 5 mM phenylmethylsulphonyl fluoride and by 90% when 0.32 mg/ml soybean trypsin inhibitor and 5 mM N-ethylmaleimide were added as well. The venom proteinase thus appears to activate inactive renin via an activation of endogenous plasma proteinases. This may be accomplished either by activation of proteinase precursors or action on proteinase inhibitor-proteinase complexes. By destroying proteinase inhibitors at the same time as it activates endogenous proteinases, Bitis arietans metalloproteinase would appear to be particularly useful for studies of the activation of inactive renin in human plasma, since endogenous proteinases are then free to activate inactive renin without subsequent inhibition by endogenous proteinase inhibitors.
已用苯甲基磺酰氟预处理并经过广泛透析的鼓腹咝蝰毒液，能够通过一种对乙二胺四乙酸（EDTA）敏感的毒液蛋白酶的作用，选择性地破坏人血浆中的蛋白酶抑制活性。我们发现，将1/5体积的这种毒液与人类血浆在25℃下孵育5小时，会导致肾素同时增加至对照值的4.4倍。10 mM的EDTA可消除无活性肾素的激活，在存在5 mM苯甲基磺酰氟时，激活速率降低50%，当同时添加0.32 mg/ml大豆胰蛋白酶抑制剂和5 mM N - 乙基马来酰亚胺时，激活速率降低90%。因此，毒液蛋白酶似乎通过激活内源性血浆蛋白酶来激活无活性肾素。这可能是通过激活蛋白酶前体或作用于蛋白酶抑制剂 - 蛋白酶复合物来实现的。通过在激活内源性蛋白酶的同时破坏蛋白酶抑制剂，鼓腹咝蝰金属蛋白酶似乎对研究人血浆中无活性肾素的激活特别有用，因为内源性蛋白酶随后可以自由激活无活性肾素，而不会受到内源性蛋白酶抑制剂的后续抑制。
