Natriuretic Peptide Receptor Type C (NPRC)

Pulmonary Arterial Hypertension Due to NPR-C Mutation: A Novel Paradigm for Normal and Pathologic Remodeling?

“…NPR-C is a disulfide-linked homodimer of a single transmembrane domain, an extracellular domain of ~440 amino acids; and a short 37 amino acid cytoplasmic domain with several inhibitory guanine nucleotide regulatory protein (Gi) activator peptide sequences that bind and activate the Gi-dependent signal transduction [16]. NPR-C has been found to lack the seven transmembrane domains of the typical G-protein-coupled receptors (GPCRs) and may thus be considered as an atypical GPCR [17]. NPR-C is widely distributed in several tissues and cells including but not limited to cardiac fibroblasts and myocytes, endothelial cells (EC) and vascular smooth muscles cells (VSMC) [16,17].…”

“…NPR-C has been found to lack the seven transmembrane domains of the typical G-protein-coupled receptors (GPCRs) and may thus be considered as an atypical GPCR [17]. NPR-C is widely distributed in several tissues and cells including but not limited to cardiac fibroblasts and myocytes, endothelial cells (EC) and vascular smooth muscles cells (VSMC) [16,17]. The binding affinity of the NPs for NPR-C is as follows: ANP > BNP > CNP [17,18].…”

“…NPR-C is widely distributed in several tissues and cells including but not limited to cardiac fibroblasts and myocytes, endothelial cells (EC) and vascular smooth muscles cells (VSMC) [16,17]. The binding affinity of the NPs for NPR-C is as follows: ANP > BNP > CNP [17,18]. Although originally classified as a clearance receptor with no signaling function, evidence suggests that NPR-C may be coupled to different intracellular signaling pathways including the adenylyl cyclase (AC)/cAMP signal transduction [16], the phospholipase C (PLC) signaling pathway, the nitric oxide (NO) pathway and Gqα/mitogen-activated protein kinase (MAPK)/PI3K and AKT pathways (As illustrated in Figure 1) [17,19,20,21].…”

“…NPs antiproliferative effects in cardiac fibroblasts may be a result of NPR-C activation [27]. In addition, NPs-induced NPR-C signal transduction has also been implicated in modulating endothelial and VSMC proliferation, endothelial permeability in coronary endothelial cells as well as L-type calcium influx [17]. These observations suggest that the NPR-C signaling pathway may play a critical role in cell proliferation via ihinhibition of MAPK signaling pathway [16].…”

“…Both heterozygous and homozygous knockout mice for Npr3 exhibit alterations in cardiovascular system, and several evidences suggest that mutations in Npr3 may lead to cardiovascular diseases [17]. Recent evidence indicates a critical role of NPR-C signaling in the pathobiology of PH.…”