Reversible activation–inactivation of renin in human plasma
Reversible activation–inactivation of renin in human plasma
复制标题
人血浆中肾素的可逆激活-失活
作者：
B. Leckie;Norah K. McGhee
肾素是一种天冬氨酸蛋白酶，切割α-球蛋白血管紧张素-收缩素原，产生十肽血管紧张素I，然后在肽酶“转化酶”的作用下转化为血管活性激素血管紧张素II。正常人血浆中存在一种非活性形式的肾素1 -3，有时称为前肾素4。暴露于pH 3.0或3.3，然后透析至中性pH，其酶活性增加。只有一小部分无活性的肾素在透析的酸性阶段被激活，大部分激活显然发生在随后透析至pH 5.7（参考文献4）或7.5（参考文献5）期间。此外，如果在血浆中加入丝氨酸蛋白酶抑制剂，透析过程中激活的非活性肾素的量就会减少4 -6。这些结果表明，酸活化是由丝氨酸蛋白酶介导的。酶如血浆激肽释放酶、纤溶酶和肾激肽释放酶作为无活性的肾素的生理激活剂的作用最近已被讨论5 -9。在我们对血浆非活性肾素激活的研究中，我们发现，与以前的报道相反，非活性肾素的完全激活发生在透析的酸性阶段。如果将血浆快速调节至pH 7.4并加热，则可逆转该活化。酸活化程序的下一步，即透析至中性pH值，使初始酸活化不可逆转。这些结果是完全出乎意料的，我们提供了一个解释，重新评估性质的非活性肾素和激活过程。
Renin, an aspartate protease, cleaves the α-globulin angioten-sinogen to produce the decapeptide angiotensin I, which is then converted to the vasoactive hormone angiotensin II by the action of a peptidase ‘converting enzyme’. An inactive form of renin1–3 sometimes termed prorenin4 is present in normal human plasma. Its enzymatic activity is increased by exposure to a pH of 3.0 or 3.3 followed by dialysis towards neutral pH. Only a small proportion of the inactive renin is activated during the acid stage of dialysis, most of the activation apparently taking place during the subsequent dialysis to pH 5.7 (ref. 4) or 7.5 (ref. 5). Furthermore, if inhibitors of serine proteases are added to the plasma, the amount of inactive renin activated by this dialysis procedure is reduced4–6. These results suggest that acid-activation is mediated by serine proteases. The role of enzymes such as plasma kallikrein, plasmin and renal kallikrein as physiological activators of inactive renin has recently been discussed5–9. In our study of the activation of plasma inactive renin we have now found that, contrary to previous reports4,5, complete activation of inactive renin takes place during the acid stage of dialysis. This activation can be reversed if plasma is rapidly adjusted to pH 7.4 and warmed. The next step in the acid-activation procedure, that is, dialysis to neutral pH, renders the initial acid-activation irreversible. These results were completely unexpected, and we offer an explanation that reassesses the nature of inactive renin and the activation process.