title: Proadrenomedullin N-terminal 20 peptide is rapidly cleaved by neutral endopeptidase.
abstract: Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide which is processed from an adrenomedullin precursor. PAMP is rapidly cleaved by human neutral endopeptidase (NEP), a protease which plays a key role in the degradation of human atrial natriuretic peptide (ANP). A double reciprocal plot indicated that Km of NEP as a substrate of PAMP was 6.1 microM and V(max) was 3.1 mmol/min/mg of NEP. EDTA, phosphoramidon and thiorphan inhibit the proteolysis of PAMP by NEP. NEP cleaves at least 6 peptide bonds in human PAMP; Arg2-Leu3, Glu8-Phe9, Lys12-Trp13, Lys15-Trp16, Trp16-Ala17 and Ala17-Leu18. The present data suggest that NEP may be involved in the circulation control by degrading PAMP as well as ANP.
authors.affiliation: First Department of Internal Medicine, Miyazaki Medical College, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nagatomo
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
authors.forename: K
authors.initials: K
authors.lastname: Kangawa
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: T
authors.initials: T
authors.lastname: Eto
mesh_terms: D053607:Adrenomedullin; D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000378:metabolism*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010455:Peptides; D011480:Protease Inhibitors / Q000494:pharmacology*; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D010446:Peptide Fragments; D010455:Peptides; D011480:Protease Inhibitors; D011506:Proteins; D053607:Adrenomedullin; D015260:Neprilysin