The intermediate form of glycine-extended adrenomedullin is the major circulating molecular form in human plasma

Adrenomedullin (AM), a potent vasodilator peptide, is processed from its AM precursor as glycine-extended AM (AM-gly), an intermediate form of AM. Subsequently, mature AM is converted from AM-gly by enzymatic amidation. Using two kinds of radioimmunoassay which recognize the entire AM molecule (E-AM-RIA) and C-terminal amide structure (C-AM-RIA), human plasma AM immunoreactivity was chromatographically characterized, In analyses of gel filtration and reverse phase high-performance liquid chromatography, most of the AIM immunoreactivity measured by E-AM-RIA was eluted at a position identical to where mature AM and AM-gly emerged and was not recognized by C-AM-RIA. These data show that immunoreactive AM measured by E-ARI-RIA is not amidated. When amidated by peptidylglycine alpha-amidating enzyme, the immunoreactive AM. was converted 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 represents immunoreactivity of AM-gly and that the concentration of immunoreactive mature AM in plasma is much lower than that of AM-gly. In practice, plasma concentration of AM-gly and mature AM: in healthy volunteers was 2.7+/-0.18 fmol/ml and 0.48+/-0.05 fmol/ml, respectively. Furthermore, plasma concentration of AM-gly and total AM was significantly elevated in patients with hypertension compared to normotensive control, The present data indicate that most of circulating plasma AM immunoreactivity is occupied by AM-gly, an intermediate form of AM, which may reflect the process of production of AM in tissues. (C) 1998 Academic Press.