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, 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.
Mentlein
R
R
Anatomisches Institut, Universität Kiel, Germany.
Roos
T
T
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001011:Aorta; D001013:Aorta, Thoracic; D001920:Bradykinin / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002268:Carboxypeptidases / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry* / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D013379:Substrate Specificity; D013552:Swine
D009478:Neuropeptide Y; D009479:Neuropeptides; D010446:Peptide Fragments; D000804:Angiotensin II; D002268:Carboxypeptidases; D010450:Endopeptidases; D000626:Aminopeptidases; D018819:Dipeptidyl Peptidase 4; D015740:Calcitonin Gene-Related Peptide; D001920:Bradykinin