Moshi M J, Zeitlin I J, Wainwright C L, Parratt J R
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, United Kingdom.
Cardiovasc Res. 1992 Apr;26(4):367-70. doi: 10.1093/cvr/26.4.367.
Canine coronary artery was recently reported to contain a cathepsin like acid optimum enzyme and a kallikrein like alkaline optimum enzyme which cleaved from a crude kininogen preparation a vasodilator uterus contracting substance. The aim of this study was to seek the presence of similar acid optimum enzymes in canine ventricular myocardium and in a large systemic artery, the aorta.
Aqueous canine tissue extracts were tested for the ability at different pHs to release uterus contracting substance (using rat isolated oestrous uterus) from a kininogen preparation. After gel filtration, the extracts were tested for the presence of arginine-amidase activity (substrate: D-Val.Leu.Arg.pNA) and enzymic activity forming bradykinin like immunoreactivity. Tissues were obtained from anaesthetised greyhounds which had been used in control studies and had received no other drug treatment.
Ventricular extracts released uterus contracting substance optimally at pH 5.2-5.4, but not at alkaline pH, neither was bradykinin like immunoreactivity formed at alkaline pH. Inhibitor studies and gel filtration showed this activity to be due to a cathepsin-D-like enzyme, molecular weight (MW) 42.6 (SD 0.9) kd, which was an arginine amidase and released bradykinin like immunoreactivity from a plasma kininogen. Aortic extracts showed two pH related peaks of uterus contracting substance formation, at pH 5.2 and (unlike myocardium) at pH 8. Also unlike myocardium, aortic extracts gave two acid optimum kininogenase peaks on gel filtration, with MW 42(4.6) kd and 252(39) kd, respectively. Both peaks released bradykinin like immunoreactivity.
Canine aorta contained an alkaline optimum and two acid optimum enzymes, while ventricle contained only a cathepsin-D-like acid optimum enzyme, all of which could form bradykinin like immunoreactivity. The ability of the ventricular enzyme to form a kinin in the slightly acid conditions of myocardial ischaemia may have a protective role.
最近有报道称犬冠状动脉含有一种组织蛋白酶样的酸最佳酶和一种激肽释放酶样的碱最佳酶，它们能从粗制激肽原制剂中裂解出一种血管舒张子宫收缩物质。本研究的目的是探寻犬心室肌和大动脉主动脉中是否存在类似的酸最佳酶。
检测犬组织水提取物在不同pH值下从激肽原制剂中释放子宫收缩物质（使用大鼠离体动情期子宫）的能力。凝胶过滤后，检测提取物中精氨酸酰胺酶活性（底物：D - 缬氨酸·亮氨酸·精氨酸·对硝基苯胺）以及形成缓激肽样免疫反应性的酶活性。组织取自用于对照研究且未接受其他药物治疗的麻醉灵缇犬。
心室提取物在pH 5.2 - 5.4时最佳释放子宫收缩物质，但在碱性pH值时不释放，在碱性pH值时也不形成缓激肽样免疫反应性。抑制剂研究和凝胶过滤表明这种活性归因于一种组织蛋白酶D样酶，分子量（MW）为42.6（标准差0.9）kd，它是一种精氨酸酰胺酶，能从血浆激肽原中释放缓激肽样免疫反应性。主动脉提取物显示出两个与pH相关的子宫收缩物质形成峰，分别在pH 5.2和（与心肌不同）pH 8。同样与心肌不同的是，主动脉提取物在凝胶过滤时有两个酸最佳激肽原酶峰，分子量分别为42(4.6) kd和252(39) kd。两个峰均释放缓激肽样免疫反应性。
犬主动脉含有一种碱最佳酶和两种酸最佳酶，而心室仅含有一种组织蛋白酶D样酸最佳酶，所有这些酶都能形成缓激肽样免疫反应性。心室酶在心肌缺血的微酸条件下形成激肽的能力可能具有保护作用。
