Atrial natriuretic peptide receptor 1 (NPR1) (NPR1)

Atrial natriuretic peptide receptor 1 (NPR1), also frequently termed Natriuretic peptide receptor A (NPR-A), is a primary transmembrane receptor responsible for mediating the physiological effects of the natriuretic peptide system. It is characterized by an extracellular ligand-binding domain and an intracellular guanylyl cyclase catalytic domain. When activated by its primary ligands, atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP), the receptor generates cyclic GMP (cGMP), a potent secondary messenger that facilitates systemic vasodilation and renal natriuresis. This signaling pathway is a critical counter-regulatory mechanism to the renin-angiotensin-aldosterone system, serving to lower blood pressure and reduce extracellular fluid volume (StatPearls: Physiology, Atrial Natriuretic Peptide). In clinical practice, NPR1 is a significant therapeutic target for the management of acute decompensated heart failure and hypertensive crises. Pharmacological agents such as Nesiritide (recombinant BNP) and Carperitide (recombinant ANP) act as direct agonists of the receptor to improve hemodynamic profiles and relieve congestion. Beyond heart failure, NPR1 signaling is increasingly studied for its roles in metabolic regulation and chronic kidney disease management. Dysregulation of this receptor is strongly associated with the pathogenesis of essential hypertension and cardiac hypertrophy. Consequently, NPR1 remain a focal point for drug development aimed at enhancing cGMP signaling to treat cardiovascular and renal pathologies (PubMed: 22442302, PubMed: 25413346).

Other names

Natriuretic peptide receptor 1Atrial natriuretic peptide receptor ANPR-AGuanylate cyclase AGC-AANPR-AGUCY2A

Atrial natriuretic peptide receptor 1 (NPR1) functions as a homodimeric transmembrane receptor with intrinsic enzymatic activity. Upon the binding of atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP) to the extracellular domain, the intracellular guanylyl cyclase domain is activated. This catalyzes the conversion of GTP to cyclic GMP (cGMP), which subsequently activates cGMP-dependent protein kinase (PKG). PKG modulates various downstream effectors to induce vascular smooth muscle relaxation and promote renal sodium and water excretion (PubMed: 25413346, UniProt: P16066).