Mentlein R, Roos T
Anatomisches Institut, Universität Kiel, Germany.
Peptides. 1996;17(4):709-20. doi: 10.1016/0196-9781(96)00066-6.
To understand the regulation of the vasoactive peptides bradykinin, angiotensin II, calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY), their proteolytic catabolism by cultured rat aortic vascular smooth muscle cells and A7r5 cells was investigated. Endopeptidase-24.11 (EC 3.4.24.11, CD 10) was responsible for the final inactivation of bradykinin, angiotensin II, and CGRP, but not of NPY, which was degraded by a different metallo-endopeptidase. Exopeptidases, namely the aminopeptidases A (EC 3.4.11.7), N (EC 3.4.11.2, CD 13), and P (EC 3.4.11.9) and the carboxypeptidases M (EC 3.4.17.12) and P (EC 3.4.17.16), were important for their differential, receptor subtype-specific activation or inactivation. Aminopeptidase A and N generated angiotensins III and IV from angiotensin II. Aminopeptidase P liberated the terminal amino acids from bradykinin and NPY, yielding the Y2 receptor specific-agonist NPY(2-36). Carboxypeptidase P produced AT II(1-7) and carboxypeptidase M produced the BK1 receptor agonist [des-Arg9]bradykinin. Thus, peptidases at the surface of vascular smooth muscle cells exert a complex influence on the level of biologically active vasoactive peptides.
为了解血管活性肽缓激肽、血管紧张素II、降钙素基因相关肽（CGRP）和神经肽Y（NPY）的调节机制，研究了培养的大鼠主动脉血管平滑肌细胞和A7r5细胞对它们的蛋白水解代谢作用。内肽酶-24.11（EC 3.4.24.11，CD 10）负责缓激肽、血管紧张素II和CGRP的最终失活，但不负责NPY的失活，NPY由另一种金属内肽酶降解。外肽酶，即氨肽酶A（EC 3.4.11.7）、N（EC 3.4.11.2，CD 13）和P（EC 3.4.11.9）以及羧肽酶M（EC 3.4.17.12）和P（EC 3.4.17.16），对它们的差异、受体亚型特异性激活或失活很重要。氨肽酶A和N从血管紧张素II生成血管紧张素III和IV。氨肽酶P从缓激肽和NPY释放末端氨基酸，产生Y2受体特异性激动剂NPY(2 - 36)。羧肽酶P产生AT II(1 - 7)，羧肽酶M产生BK1受体激动剂[去-Arg9]缓激肽。因此，血管平滑肌细胞表面的肽酶对生物活性血管活性肽的水平产生复杂影响。
