Kinin- and angiotensin-converting enzyme (ACE) inhibitor-mediated nitric oxide production in endothelial cells.
Carboxypeptidase cleavage of the C-terminal Arg of kinins generates specific agonists of the B1 receptor. Activation of B1 receptors produces nitric oxide via eNOS in bovine endothelial cells and iNOS in cytokine-stimulated human endothelial cells. Angiotensin-converting enzyme (ACE) inhibitors are direct agonists of B1 receptors in endothelial cells, although they release NO via a different signaling pathway than peptide ligands in bovine cells. This brief review discusses carboxypeptidase M as a required processing enzyme for generating B1 agonists, how ACE inhibitors and peptide ligands stimulate NO production and the evidence for, as well as some consequences of, the direct activation of B1 receptors by ACE inhibitors.
Skidgel
Randal A
RA
Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA. rskidgel@uic.edu
Stanisavljevic
Sinisa
S
Erdös
Ervin G
EG
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D058851:GPI-Linked Proteins; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D043783:Receptor, Bradykinin B1 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D058851:GPI-Linked Proteins; D043783:Receptor, Bradykinin B1; D009569:Nitric Oxide; C058479:carboxypeptidase M; D008666:Metalloendopeptidases