HYDROLYSIS OF IODINE-LABELED URODILATIN AND ANP BY RECOMBINANT NEUTRAL ENDOPEPTIDASE EC.3.4.24.11

1 Urodilatin is a 32 amino-acid peptide of similar sequence to atrial natriuretic peptide (ANP), with four additional amino-acids at the N-t erminus. Although ANP and urodilatin bind to the same receptors with s imilar affinities, urodilatin is more active than ANP as a natriuretic agent. Previous studies, using neutral endopeptidase EC 3.4.24.11 (NE P) derived from crude membrane preparations, were inconclusive, but su ggested that urodilatin was more resistant than ANP to degradation by this enzyme. In the present study, we compared the degradation rates o f [I-125]-urodilatin and [I-125]-ANP by pure recombinant NEP (rNEP). 2 Incubation of radioactively labelled ANP with rNEP resulted in a much more rapid degradation of the peptide than that for labelled urodilat in. 3 Both phosphoramidon and SQ-28,603, potent inhibitors of NEP, com pletely protected both peptides from metabolism by rNEP. 4 The circula r dichroism spectra of the two peptides indicate that they are very si milar and exist largely in unordered or flexible conformations. 5 Thes e results support the relative resistance of urodilatin to NEP, and in dicate that urodilatin may be of use as a therapeutic agent, in condit ions in which ANP is ineffective.