Metabolism of endothelin‐1 and big endothelin‐1 by recombinant neutral endopeptidase EC.3.4.24.11

• Published in: British journal of pharmacology 1993-08, Vol.109 (4), p.1024-1028
• Main Authors: Abassi, Zaid A., Golomb, Eliahu, Bridenbaugh, Robert, Keiser, Harry R.
• Format: Article
• Language: English
• Subjects: Alanine - analogs & derivatives; Analytical, structural and metabolic biochemistry; big‐endothelin‐1 [1–38]; Biological and medical sciences; Chromatography, High Pressure Liquid; DNA, Complementary - metabolism; Endothelin-1; Endothelins - metabolism; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Glycopeptides - pharmacology; h.p.l.c; Humans; Hydrolases; In Vitro Techniques; Iodine Radioisotopes; Neprilysin - antagonists & inhibitors; Neprilysin - metabolism; Neprilysin - pharmacology; neutral endopeptidase inhibitors; phosphoramidon; Protein Precursors - metabolism; recombinant neutral endopeptidase; Recombinant Proteins - metabolism; SQ‐28,603
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1993.tb13724.x

1 Inhibitors of neutral endopeptidase EC.3.4.24.11 (NEP) have been shown to attenuate the hypertensive effect of big‐endothelin‐1 (BET‐1) in rats. To determine whether NEP converts BET‐1 to endothelin‐1 (ET‐1), the effect of a recombinant NEP (rNEP) on BET‐1 and on ET‐1 was assessed in vitro. 2 Incubation of [125I]‐ET‐1 with 1 μg ml−1 of rNEP resulted in degradation of the peptide within minutes. Increase in the amount of rNEP to 10 μg ml−1 led to total cleavage of [125I]‐ET‐1 within seconds. 3 Phosphoramidon (10 μm) or SQ‐28,603 (100 μm) totally suppressed the degradation of [125I]‐ET‐1 by rNEP. 4 The degradation of [125I]‐BET‐1 by either 1 or 10 μg ml−1 of rNEP was much slower than that of [125I]‐ET‐1. Again, both phosphoramidon and SQ 28,603 protected the peptide from degradation. 5 Intact [125I]‐ET‐1 was not observed when [125I]‐BET‐1 was incubated with rNEP. 6 These data show that neutral endopeptidase EC.3.4.24.11 is not an endothelin converting enzyme.