Role of endopeptidase-24.11 in the inactivation of atrial natriuretic peptide.

The circulating form of atrial natriuretic factor is a 28-residue peptide containing a 17-residue disulphide-linked ring. It has important actions on the kidney, largely on its haemodynamics, and at other sites including the adrenal cortex and CNS. It has a short half-life in vivo and is rapidly inactivated when incubated with kidney microvillar membranes. Of the battery of peptidases present in that membrane, only one, endopeptidase-24.11, is responsible for initiating the attack, and this commences with hydrolysis of the Cys7-Phe8 bond within the ring. Hydrolysis at this and other points has been shown to inactivate the peptide and this information has pointed the way to the synthesis of resistant analogues.