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

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Abstract
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.

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