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 inh ibited by EDTA and 1,10 phenanthroline but not by phosphoramidon, leup eptin and pepstatin. The above data are consistent with initial hydrol ysis adjacent to hydrophobic residues by a metalloprotease, generating ADM(8-52), (26-52) and(33-52), followed by an aminopeptidase action t o produce ADM(2-52), (27-52) and (28-52). Improved understanding of th e metabolism of ADM may have therapeutic implications, for example in the treatment of heart failure. (C) 1997 Elsevier Science Inc.