Degradation of atrial natriuretic peptides by an enzyme in rat kidney resembling neutral endopeptidase 24.11.
The inactivation of rat atrial natriuretic factor (ANF) was studied using a bioassay, ANF-stimulated guanylate cyclase activity. Rat kidney membranes degraded ANF into biologically inactive forms. The primary cleavage site appears to be the Cys105-Phe106 bond. The degradation, measured by HPLC, followed classical Michaelis-Menten kinetics. The sensitivity of the enzyme to inhibitors suggested it to be a metalloendopeptidase, resembling neutral endopeptidase 24.11. When this enzyme, characterised by its enkephalin-degrading activity, was compared to the enzyme responsible for ANF inactivation, striking differences were found in tissue distribution, pH-dependence and sensitivity to protein-modifying reagents. It is concluded that an enzyme similar to endopeptidase 24.11 may be responsible for inactivation of atrial peptides in the rat.
Bertrand
P
P
Centre de Recherche de Gennevilliers, France.
Doble
A
A
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000201:enzymology*; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D009320:Atrial Natriuretic Factor; D015260:Neprilysin