THE INTERMEDIATE FORM OF GLYCINE-EXTENDED ADRENOMEDULLIN IS THE MAJORCIRCULATING MOLECULAR-FORM IN HUMAN PLASMA

Adrenomedullin (AM), a potent vasodilator peptide, is processed from i ts AM precursor as glycine-extended AM (AM-gly), an intermediate form of AM. Subsequently, mature AM is converted from AM-gly by enzymatic a midation. Using two kinds of radioimmunoassay which recognize the enti re AM molecule (E-AM-RIA) and C-terminal amide structure (C-AM-RIA), h uman plasma AM immunoreactivity was chromatographically characterized, In analyses of gel filtration and reverse phase high-performance liqu id chromatography, most of the AIM immunoreactivity measured by E-AM-R IA was eluted at a position identical to where mature AM and AM-gly em erged and was not recognized by C-AM-RIA. These data show that immunor eactive AM measured by E-ARI-RIA is not amidated. When amidated by pep tidylglycine alpha-amidating enzyme, the immunoreactive AM. was conver ted to a form that can be detected by C-AM-RIA. These results indicate that most of the total AM. immunoreactivity measured by E-AM-RIA repr esents immunoreactivity of AM-gly and that the concentration of immuno reactive mature AM in plasma is much lower than that of AM-gly. In pra ctice, plasma concentration of AM-gly and mature AM: in healthy volunt eers was 2.7+/-0.18 fmol/ml and 0.48+/-0.05 fmol/ml, respectively. Fur thermore, plasma concentration of AM-gly and total AM was significantl y elevated in patients with hypertension compared to normotensive cont rol, The present data indicate that most of circulating plasma AM immu noreactivity is occupied by AM-gly, an intermediate form of AM, which may reflect the process of production of AM in tissues. (C) 1998 Acade mic Press.