Delayed metabolism of human brain natriuretic peptide reflects resistance to neutral endopeptidase

• DOI: 10.1677/joe.0.1670239
• Publication Date: 2004-12-02T23:42:13Z
• Authors: MW Smith; EA Espiner; TG Yandle; CJ Charles; AM Richards
• Keywords: Atrial natriuretic peptide; Brain natriuretic peptide; Endopeptidase

Metabolism of natriuretic peptides is regulated by two degradative pathways: uptake the clearance receptor (natriuretic peptide C--NPR-C) and hydrolysis neutral endopeptidase (NEP). Affinity studies favour a dominant role NPR-C in hormone degradation several species but do not account for efficacy NEP inhibitors vivo, nor uniquely prolonged half life (t((1/2))) human brain (hBNP). Postulating that (1) delayed metabolism hBNP reflects resistance to (2) interactions between increase enzyme activity, we have used purified ovine NEP, plus lung plasma membranes study relative importance pathways. We also related findings vivo. Binding affinities atrial (ANP), BNP (oBNP) oNPR-C were similar (K(d)=8-16 pM). In contrast, unlike ANP oBNP, was significantly degraded oNEP or membranes. Despite (and high) affinity oBNP hBNP, t((1/2)) (12.7 min) more than fourfold (2.6 min). Although found no evidence receptor-enzyme interaction, our results show NEP. These important implications future treatment strategies disease.