Zeitlin I J, Fagbemi S O, Parratt J R
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland.
Cardiovasc Res. 1989 Feb;23(2):91-7. doi: 10.1093/cvr/23.2.91.
The presence of amidases cleaving the tripeptide VAL.LEU.ARG.pNA, and liberating from human plasma kininogen substance(s) able to contract uterine smooth muscle and to lower blood pressure (uterus contracting and hypotensive activity), has been demonstrated in vascular and muscle tissues from normally perfused and ischaemic areas of dog hearts. Studies were carried out on blood free preparations of coronary arteries and veins and normally perfused and ischaemic ventricle. All the tissues were found to contain both acid optimum (pH 6) and alkaline optimum (pH greater than 9) enzymes forming uterus contracting substance (UCS, bioassayed on isolated uterus of rats in oestrus), the highest levels of both activities being found in arterial tissues and the least in ventricle. Enzyme levels in ischaemic or normally perfused ventricle did not differ significantly. Gel filtration (Sephacryl, S-300) of coronary artery extracts gave one peak each of acid optimum enzyme with a molecular weight of 38,300 +/- 800 daltons and alkaline optimum enzyme with a molecular weight of 92,100 +/- 4000 daltons. Both acid and alkaline enzyme fractions cleaved the tripeptide substrate with pH optima identical to those for UCS formation. The acid optimum activity, both of UCS formation and tripeptide cleavage, was inhibited by pepstatin but not by aprotinin or soybean trypsin inhibitor (SBTI). The alkaline optimum activity was inhibited by aprotinin and SBTI but not pepstatin. Both acid and alkaline optimum enzymes released a hypotensive agent from a plasma protein substrate. The molecular weight and response to inhibitors of the acid optimum enzyme were similar to a cathepsin, and those of the alkaline optimum enzyme were similar to plasma kallikrein.
在犬心脏正常灌注和缺血区域的血管及肌肉组织中，已证实存在酰胺酶，该酶可裂解三肽VAL.LEU.ARG.pNA，并从人血浆激肽原中释放出能够使子宫平滑肌收缩并降低血压的物质（子宫收缩和降压活性）。对冠状动脉和静脉的无血制剂以及正常灌注和缺血的心室进行了研究。发现所有组织均含有形成子宫收缩物质（UCS，在发情期大鼠离体子宫上进行生物测定）的最适酸性（pH 6）和最适碱性（pH大于9）酶，两种活性的最高水平见于动脉组织，最低水平见于心室。缺血或正常灌注心室中的酶水平无显著差异。冠状动脉提取物的凝胶过滤（Sephacryl，S - 300）分别给出了一个最适酸性酶峰，其分子量为38,300±800道尔顿，以及一个最适碱性酶峰，其分子量为92,100±4000道尔顿。酸性和碱性酶组分裂解三肽底物的最适pH与形成UCS的最适pH相同。抑肽酶可抑制UCS形成和三肽裂解的最适酸性活性，但抑肽酶或大豆胰蛋白酶抑制剂（SBTI）则无此作用。最适碱性活性可被抑肽酶和SBTI抑制，但不受胃蛋白酶抑制剂抑制。最适酸性和碱性酶均可从血浆蛋白底物中释放出一种降压剂。最适酸性酶的分子量和对抑制剂的反应与组织蛋白酶相似，最适碱性酶的分子量和对抑制剂的反应与血浆激肽释放酶相似。
