Atrial natriuretic peptide receptor 3 (NPR3)

Atrial natriuretic peptide receptor 3 (NPR3), also known as natriuretic peptide receptor C (NPR-C), is a transmembrane protein that serves as the primary clearance receptor for the natriuretic peptide family, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) (UniProt P17342). Unlike NPR1 and NPR2, NPR3 lacks an intracellular guanylyl cyclase domain and instead functions to regulate the systemic and local concentrations of these peptides through receptor-mediated endocytosis and subsequent lysosomal degradation (PubMed: 21641545). Beyond its role in clearance, NPR3 is known to couple with inhibitory G proteins (Gi), which leads to the inhibition of adenylyl cyclase and the modulation of various intracellular signaling pathways (PubMed: 10523645). In the cardiovascular system, NPR3 is a critical regulator of blood pressure and fluid volume; its genetic variants and expression levels have been linked to hypertension, heart failure, and obesity (PubMed: 25630451). Pharmacological targeting of NPR3, particularly through the use of small-molecule antagonists like M372049, is an emerging therapeutic strategy aimed at increasing the bioavailability of endogenous natriuretic peptides to provide cardioprotective and renoprotective effects (PubMed: 11524394). Additionally, NPR3 plays a role in bone growth regulation by modulating CNP levels, making it a target of interest in skeletal disorders (PubMed: 18258921).

Other names

Natriuretic peptide receptor CNPR-CANPR-CAtrial natriuretic peptide clearance receptor

Antagonism of the clearance receptor to increase levels of endogenous natriuretic peptides.