What is the Origin of Neprilysin?

The enzyme was originally named neutral endopeptidase due to its optimal activity at a neutral pH. The later name, neprilysin, was derived from its ability to degrade neuropeptides. Its clinical significance became fully realized when pharmaceutical research targeted its inhibitory potential to enhance the effects of endogenous cardioprotective hormones. The term now stands for a crucial regulatory node in the neurohormonal control of cardiovascular and renal function.

What is the Mechanism of Neprilysin?

Neprilysin operates by hydrolyzing the peptide bonds of its substrates, effectively cleaving the active peptide into inactive fragments. The enzyme is strategically located on the cell membranes of various tissues, including the kidneys, lungs, and heart. By rapidly degrading natriuretic peptides, bradykinin, and substance P, neprilysin limits their duration of action. Therapeutic inhibition of neprilysin, therefore, increases the half-life and circulating concentration of these beneficial peptides, leading to sustained diuresis, reduced plasma volume, and a decrease in systemic vascular resistance.

Neprilysin ∞ Area

Neprilysin

Meaning

Neprilysin, also known as neutral endopeptidase (NEP), is a ubiquitous cell-surface enzyme that functions as a peptidase, responsible for degrading a wide variety of endogenous vasoactive peptides. Its primary physiological role is the inactivation of natriuretic peptides (NPs), which are hormones released by the heart and brain to promote vasodilation and natriuresis, thereby lowering blood pressure. In the hormonal health and cardiovascular context, inhibition of neprilysin is a therapeutic strategy to potentiate the beneficial effects of NPs, improving outcomes in patients with heart failure. The enzyme is a key regulator of the balance between vasoconstriction and vasodilation.