Natriuretic peptide receptor 3 (NPR3) (NPR3)

The Natriuretic peptide receptor 3 (NPR3), historically identified in guinea pig lung tissue as an NPR-like binding site, is a single-pass transmembrane protein that serves as the primary clearance receptor for natriuretic peptides (PubMed: 2527127). Unlike the signaling receptors NPR1 and NPR2, NPR3 lacks an intracellular guanylyl cyclase domain and instead functions to regulate the circulating levels of atrial, brain, and C-type natriuretic peptides through receptor-mediated endocytosis and subsequent lysosomal degradation (UniProt: P21729). In addition to its clearance role, NPR3 is known to couple with inhibitory G-proteins (Gi) to modulate adenylyl cyclase activity, thereby influencing various intracellular signaling pathways (PubMed: 15837019). In the lung, NPR3 is highly expressed and plays a vital role in maintaining vascular homeostasis and fluid balance by controlling the local availability of natriuretic peptides (PubMed: 2161580). Pharmacological modulation of NPR3 is a therapeutic strategy aimed at increasing the half-life of endogenous natriuretic peptides to treat cardiovascular and pulmonary diseases (PubMed: 11591457).

Other names

Natriuretic peptide receptor CNPR-CAtrial natriuretic peptide receptor type CANP clearance receptorGuinea-pig lung NPR-like siteGUCY2B

Acts as a clearance receptor by internalizing natriuretic peptides for degradation and inhibits adenylyl cyclase through Gi protein coupling.