Natriuretic peptide receptor type-C (NPR-C)

Natriuretic peptide receptor type-C (NPR-C), also known as NPR3, is a single-transmembrane protein that serves as a primary regulator of the natriuretic peptide system [1, 5]. Unlike the related receptors NPR-A and NPR-B, NPR-C lacks intrinsic guanylyl cyclase activity and was historically characterized as a clearance receptor that internalizes and degrades atrial, B-type, and C-type natriuretic peptides (ANP, BNP, and CNP) to modulate their systemic concentrations [4, 8]. However, it is now recognized as a signaling receptor coupled to inhibitory G proteins (Gi), through which it inhibits adenylyl cyclase and activates phospholipase C pathways [6, 10]. NPR-C plays a critical role in cardiovascular homeostasis, renal function, lipid metabolism, and endochondral bone growth [1, 13]. Pathological alterations in NPR-C expression or function are associated with hypertension, heart failure, obesity, and atherosclerosis [7, 15, 17]. Pharmacological modulation of NPR-C, either through selective agonists to trigger its signaling pathways or by inhibiting its clearance function to prolong the half-life of beneficial endogenous natriuretic peptides, represents a promising therapeutic avenue for treating cardiovascular and metabolic disorders [11, 12].

Other names

NPR3Natriuretic peptide receptor 3ANP-CANPR-CANPRCGUCY2BAtrial natriuretic peptide clearance receptorAtrionatriuretic peptide receptor C

NPR-C acts as a clearance receptor by binding natriuretic peptides (ANP, BNP, CNP) and internalizing them via clathrin-mediated endocytosis for lysosomal degradation [5, 8]. It also functions as a signaling receptor by coupling to inhibitory G proteins (Gi), which leads to the inhibition of adenylyl cyclase (reducing cAMP levels) and the activation of phospholipase C-beta [6, 10, 14].