title: The intermediate form of glycine-extended adrenomedullin is the major circulating molecular form in human plasma.
abstract: 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 AM 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-AM-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.
authors.affiliation: First Department of Internal Medicine, Miyazaki Medical College, Kiyotake, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
authors.forename: J
authors.initials: J
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Kawamoto
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: N
authors.initials: N
authors.lastname: Chino
authors.forename: K
authors.initials: K
authors.lastname: Kangawa
authors.forename: T
authors.initials: T
authors.lastname: Eto
mesh_terms: D053607:Adrenomedullin; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005998:Glycine / Q000737:chemistry; D006801:Humans; D006973:Hypertension / Q000097:blood; D007120:Immunochemistry; D010455:Peptides / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D011499:Protein Processing, Post-Translational; D011863:Radioimmunoassay; D014665:Vasodilator Agents / Q000097:blood* / Q000737:chemistry / Q000276:immunology
chemical_list: D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin; D005998:Glycine