NPR-A

Natriuretic peptide receptor NPR-A (GC-A/NPR1) is a transmembrane guanylyl cyclase that converts natriuretic peptide binding into intracellular cGMP signaling^[1]. ANP and BNP activate NPR-A to regulate blood pressure, blood volume, natriuresis, and cardiac hypertrophy^[1][2]. Mechanistically, ANP-NPR-A signaling increases cGMP and suppresses PKC activation in vascular smooth muscle cells through cGMP-dependent protein kinase^[3]. In disease models, Npr1 disruption causes hypertension, cardiac hypertrophy, interstitial fibrosis, and pressure-independent enhancement of hypertrophic remodeling^[2][4][5]. Compared with related isoforms, NPR-A and NPR-B function as guanylyl cyclase receptors, whereas NPR-C lacks intrinsic enzymatic activity and controls peptide availability through internalization and degradation^[1]. NPR-A mainly mediates ANP/BNP responses, while NPR-B contributes substantial CNP-responsive guanylyl cyclase activity and becomes predominant in failing mouse hearts^[6]. For experimental applications, NPR-A agonist responses can be monitored through cGMP production, and the NPR-A antagonist A-71915 blocks ANP-induced cGMP generation and downstream PKC inhibition^[3]. NPR-A/NPR-B desensitization can occur without receptor internalization, supporting direct signaling assays rather than assuming ligand-induced receptor loss^[7].