Human Natriuretic Peptide Receptor 3 (NPR3) Protein

Background

NPR3, also known as the natriuretic peptide clearance receptor, binds all three natriuretic peptides (ANP, BNP, and CNP) but does not have intrinsic guanylyl cyclase activity. Instead, NPR3 functions as a clearance receptor, removing natriuretic peptides from circulation and modulating their bioavailability and effects. NPR3 is expressed in various tissues, including the heart, kidney, and vascular system, where it regulates peptide levels to maintain cardiovascular and renal homeostasis. NPR3's role in limiting natriuretic peptide activity impacts blood pressure regulation, vascular remodeling, and fluid balance. Genetic polymorphisms in NPR3 have been linked to hypertension, heart failure, and obesity, highlighting its role in metabolic and cardiovascular health. In addition to clearance, NPR3 signaling influences cellular processes through its ability to couple with inhibitory G proteins, affecting cAMP levels and downstream pathways. NPR3-mediated clearance of CNP is critical for controlling vascular tone and endothelial function, underscoring its regulatory importance. Recent studies suggest that modulating NPR3 activity could enhance natriuretic peptide signaling, offering therapeutic potential for managing cardiovascular and metabolic disorders.