Identification of protease 3.4.24.11 as the major atrial natriuretic factor degrading enzyme in the rat kidney

Peptides. Jan-Feb 1988;9(1):173-80. doi: 10.1016/0196-9781(88)90024-1.

Abstract

We have identified a metalloendoprotease from rat kidney cortex that cleaves the cysteine-phenylalanine bond (Cys7-Phe8) within the 17 amino acid ring structure of atrial natriuretic factor (ANF). Cleavage at this site represents the major ANF degradative activity in rat kidney, and is inhibited by the known metalloendoprotease inhibitors, thiorphan, phosphoramidon and zincov with IC50 values in the nanomolar range. Since these are specific inhibitors of protease 3.4.24.11, both protease 3.4.24.11 and ANF degrading activities were monitored during purification. Both activities copurified at each chromatographic step. Furthermore, purified protease 3.4.24.11 cleaved ANF specifically at the Cys7-Phe8 bond. It is concluded from this work that the major ANF degrading enzyme in rat kidney is protease 3.4.24.11.

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / metabolism*
  • Chromatography, Affinity
  • Chromatography, DEAE-Cellulose
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Electrophoresis, Polyacrylamide Gel
  • In Vitro Techniques
  • Kidney Cortex / enzymology*
  • Male
  • Metalloendopeptidases / isolation & purification*
  • Metalloendopeptidases / metabolism
  • Molecular Weight
  • Neprilysin
  • Rats
  • Rats, Inbred Strains

Substances

  • atrial natriuretic peptide, rat
  • Atrial Natriuretic Factor
  • Metalloendopeptidases
  • Neprilysin