Metabolism of endothelin-1 and big endothelin-1 by recombinant neutral endopeptidase EC.3.4.24.11
| Autor: | Eliahu Golomb, Robert Bridenbaugh, Harry R. Keiser, Zaid Abassi |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
medicine.hormone
DNA Complementary Peptide In Vitro Techniques Pharmacology Iodine Radioisotopes Endothelins chemistry.chemical_compound medicine Humans Protein Precursors Neprilysin Chromatography High Pressure Liquid chemistry.chemical_classification Alanine Endothelin-1 Phosphoramidon Glycopeptides Endothelin 1 Molecular biology Recombinant Proteins Endopeptidase Enzyme chemistry Endothelin receptor Research Article |
| Zdroj: | British Journal of Pharmacology. 109:1024-1028 |
| ISSN: | 0007-1188 |
| Popis: | 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 microgram ml-1 of rNEP resulted in degradation of the peptide within minutes. Increase in the amount of rNEP to 10 micrograms ml-1 led to total cleavage of [125I]-ET-1 within seconds. 3. Phosphoramidon (10 microM) or SQ-28,603 (100 microM) totally suppressed the degradation of [125I]-ET-1 by rNEP. 4. The degradation of [125I]-BET-1 by either 1 or 10 micrograms 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. |
| Databáze: | OpenAIRE |
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