Degradation of human adrenomedullin(1-52) by plasma membrane enzymes and identification of metabolites.
Very little is known about degradation or metabolism of adrenomedullin. To this end, we incubated adrenomedullin with ovine adrenal, kidney and lung plasma membrane preparations and showed the major degradation products were ADM(2-52) and ADM(8-52). Smaller amounts of ADM(26-52), (27-52), (28-52) and (33-52) were also produced. Degradation was inhibited by EDTA and 1,10 phenanthroline but not by phosphoramidon, leupeptin and pepstatin. The above data are consistent with initial hydrolysis adjacent to hydrophobic residues by a metalloprotease, generating ADM(8-52), (26-52) and (33-52), followed by an aminopeptidase action to produce ADM(2-52), (27-52) and (28-52). Improved understanding of the metabolism of ADM may have therapeutic implications, for example in the treatment of heart failure.
Lewis
L K
LK
Department of Endocrinology, Christchurch Hospital, New Zealand. LLewis@CHMEDS.AC.NZ
Smith
M W
MW
Brennan
S O
SO
Yandle
T G
TG
Richards
A M
AM
Nicholls
M G
MG
D000311:Adrenal Glands / Q000201:enzymology; D053607:Adrenomedullin; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D007668:Kidney / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008969:Molecular Sequence Data; D010455:Peptides / Q000187:drug effects / Q000378:metabolism*; D012756:Sheep
D004791:Enzyme Inhibitors; D010455:Peptides; D053607:Adrenomedullin