PROTEASES INVOLVED IN THE METABOLISM OF ANGIOTENSIN-II, BRADYKININ, CALCITONIN-GENE-RELATED PEPTIDE (CGRP), AND NEUROPEPTIDE-Y BY VASCULAR SMOOTH-MUSCLE CELLS

To understand the regulation of the vasoactive peptides bradykinin, an giotensin 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 o f bradykinin, angiotensin II, and CGRP, but not of NPY, which was degr aded by a different metallo-endopeptidase. Exopeptidases, namely the a minopeptidases 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 acti vation or inactivation. Aminopeptidase A and N generated angiotensins III and IV from angiotensin II. Aminopeptidase P liberated the termina l amino acids from bradykinin and NPY, yielding the Y-2 receptor speci fic-agonist NPY(2-36). Carboxypeptidase P produced AT II(1-7) and carb oxypeptidase M produced the BK1 receptor agonist [des-Arg(9)]bradykini n. Thus, peptidases at the surface of vascular smooth muscle cells exe rt a complex influence on the level of biologically active vasoactive peptides.