Vascular, plasma membrane aminopeptidase M. Metabolism of vasoactive peptides.
Aminopeptidase M (EC 3.4.11.2), an enzyme present on the cell surface of vascular endothelium and/or smooth muscle, rapidly hydrolyzes leucyl- and arginyl-2-naphthylamides and a number of vasoactive peptides at physiologic pH. Utilizing both thin-layer chromatography and high pressure liquid chromatography, it was found that vascular aminopeptidase M converted kallidin to bradykinin and inactivated des(Asp1)angiotensin I, angiotensin III, hepta(5-11)substance P and hexa(6-11)substance P. Aminopeptidase M did not, however, hydrolyze bradykinin, angiotensin I, angiotensin II, saralasin, vasopressin, oxytocin or any form of substance P containing a component of the Arg-Pro-Lys-Pro sequence. Both the naphthylamidase and peptidase activities were inhibited similarly by known amino-peptidase M inhibitors including o-phenanthroline, amastatin, bestatin and puromycin. However, inhibitors of angiotensin I converting enzyme (captopril), carboxypeptidase N (MERGETPA), neutral endopeptidase (phosphoramidon), post proline cleaving enzyme and dipeptidyl(amino)peptidase IV (diisopropylphosphofluoridate, DFP) were without effect. These results demonstrate that vascular, cell surface aminopeptidase M can selectively metabolize vasoactive peptides and may play a role in modulating their levels in the circulation and/or within the vessel wall.
Palmieri
F E
FE
Petrelli
J J
JJ
Ward
P E
PE
D000626:Aminopeptidases / Q000378:metabolism*; D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000201:enzymology*; D018826:CD13 Antigens; D002462:Cell Membrane / Q000201:enzymology; D066298:In Vitro Techniques; D007705:Kinins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D013373:Substance P / Q000378:metabolism; D013379:Substrate Specificity; D013552:Swine
D000809:Angiotensins; D007705:Kinins; D010446:Peptide Fragments; D010455:Peptides; D013373:Substance P; D000626:Aminopeptidases; D018826:CD13 Antigens; D007703:Peptidyl-Dipeptidase A