Proadrenomedullin N-terminal 20 peptide is rapidly cleaved by neutral endopeptidase

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 mu M and Vmax 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; Arg(2)-Leu(3), Glu(8)-Phe(9), Lys(12)-Trp(13), Lys(15)-Trp(16), Trp(16)-Ala(17) and Ala(17)-Leu(18). The present data suggest that NEP may be involved in the circulation control by degrading RAMP as well as ANP. (C) 1996 Academic Press, Inc.