一种从人血清蛋白产生的新型激肽增强肽的药理特性。

Pharmacological properties of a new kinin-potentiating peptide generated from human serum proteins.

作者信息

Assreuy J, Almeida A A, Guimarães J A

机构信息

Department of Biochemistry, Universidade Federal do Rio de Janeiro, Brazil.

出版信息

Eur J Pharmacol. 1989 Sep 13;168(2):231-7. doi: 10.1016/0014-2999(89)90569-4.

DOI:10.1016/0014-2999(89)90569-4

PMID:2606151

Abstract

A kinin-potentiating peptide (KPP) generated from human plasma proteins on trypsin incubation was partially purified by ultrafiltration and ion-exchange chromatography and was characterized through some of its pharmacological properties. KPP itself was devoid of any action but it potentiated the guinea-pig ileum contractions elicited by several kinins, including an analog resistant to angiotensin-converting enzyme (ACE). In contrast, contractions induced by angiotensin II, histamine, acetylcholine, barium chloride and substance P were not potentiated. Not only did KPP have high specificity towards kinins, but its action started immediately and induced kinin potentiation in a dose-dependent and reversible manner. Furthermore KPP potentiated the bradykinin contracting effects on the rat uterus, a preparation with very poor ACE activity, and on guinea-pig ileum previously incubated with 1.10-phenanthroline, a metal chelator able to inhibit ACE and kininase I activities and with phosphoramidon, a specific inhibitor of neutral endopeptidase (NEP). The results suggest that the potentiating effect of KPP is due to a mechanism different from the inhibition of kinin metabolism by ACE, NEP and kininase I.

摘要

在胰蛋白酶作用下从人血浆蛋白产生的一种激肽增强肽（KPP），通过超滤和离子交换色谱法进行了部分纯化，并通过其一些药理特性进行了表征。KPP本身没有任何作用，但它增强了几种激肽引起的豚鼠回肠收缩，包括一种对血管紧张素转换酶（ACE）有抗性的类似物。相比之下，血管紧张素II、组胺、乙酰胆碱、氯化钡和P物质诱导的收缩没有增强。KPP不仅对激肽具有高度特异性，而且其作用立即开始，并以剂量依赖性和可逆方式诱导激肽增强。此外，KPP增强了缓激肽对大鼠子宫（一种ACE活性非常低的标本）以及对先前用1,10-菲咯啉（一种能够抑制ACE和激肽酶I活性的金属螯合剂）和磷酰胺（一种中性内肽酶（NEP）的特异性抑制剂）孵育过的豚鼠回肠的收缩作用。结果表明，KPP的增强作用是由于一种不同于ACE、NEP和激肽酶I对激肽代谢抑制的机制。