Human Atrial Natriuretic Peptide Receptor 1 (NPR1) Protein

Background

NPR1 is a guanylate cyclase-linked receptor that binds atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), mediating their effects on vascular homeostasis, natriuresis, and diuresis. Upon ligand binding, NPR1 undergoes conformational changes that activate its intracellular guanylyl cyclase domain, producing cyclic GMP (cGMP), a second messenger that regulates vasodilation, blood pressure, and renal salt excretion. NPR1 is primarily expressed in vascular endothelial cells, renal tubular cells, and cardiac tissue, where it plays a pivotal role in maintaining cardiovascular and renal function. Mutations or dysregulation of NPR1 are associated with hypertension, heart failure, and other cardiovascular disorders due to impaired natriuretic signaling. Structural analyses reveal that NPR1 consists of an extracellular ligand-binding domain, a transmembrane region, and an intracellular guanylyl cyclase domain, highlighting its complex regulatory mechanisms. NPR1 also interacts with protein kinases and phosphodiesterases, fine-tuning the cGMP signaling cascade. In addition to cardiovascular effects, NPR1 signaling influences adipose tissue metabolism and has been linked to lipid regulation and energy homeostasis. Emerging research suggests that NPR1 activation could be a therapeutic target for managing hypertension and heart failure by enhancing natriuretic peptide activity.