Bradykinin-degrading enzymes: structure, function, distribution, and potential roles in cardiovascular pharmacology.
Bradykinin is susceptible to degradation by a variety of endo- and exopeptidases. These include aminopeptidase P, meprin, endopeptidase 24.15, prolyl endopeptidase, neutral endopeptidase 24.11, angiotensin I-converting enzyme, carboxypeptidase N, carboxypeptidase M, and deamidase. These peptidases are widely distributed in various tissues and cells in the body, and their subcellular locations vary as well. Because bradykinin is inactivated (for binding the B2 receptor) when any of its peptide bonds are cleaved, all of these enzymes qualify as potential "kininases" in vivo; however, the importance of a particular enzyme as a kininase will depend on its localization, access to bradykinin, and the presence of other peptidases. In addition, these peptidases can cleave a variety of other peptide hormone substrates. Determination of the importance of a peptidase in the inactivation of bradykinin during a particular physiological response can be difficult, but specific peptidase inhibitors and kinin receptor antagonists are useful tools in investigating these questions.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001920:Bradykinin / Q000378:metabolism*; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D020689:Exopeptidases; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*
D010450:Endopeptidases; D020689:Exopeptidases; D010447:Peptide Hydrolases; D001920:Bradykinin