Selective Activation of the B Natriuretic Peptide Receptor by C-Type Natriuretic Peptide (CNP)

Abstract

The natriuretic peptides are hormones that can stimulate natriuretic, diuretic, and vasorelaxant activity in vivo, presumably through the activation of two known cell surface receptor guanylyl cyclases (ANPR-A and ANPR-B). Although atrial natriuretic peptide (ANP) and, to a lesser extent, brain natriuretic peptide (BNP) are efficient activators of the ANPR-A guanylyl cyclase, neither hormone can significantly stimulate ANPR-B. A member of this hormone family, C-type natriuretic peptide (CNP), potently and selectively activated the human ANPR-B guanylyl cyclase. CNP does not increase guanosine 3',5'-monophosphate accumulation in cells expressing human ANPR-A. The affinity of CNP for ANPR-B is 50- or 500-fold higher than ANP or BNP, respectively. This ligand-receptor pair may be involved in the regulation of fluid homeostasis by the central nervous system.

Cardiomyocyte‐restricted over‐expression of C‐type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice

“…Furthermore, chronic volume overload by an infrarenal aortocaval shunt in 8-week-old rats resulted in exaggerated cardiac hypertrophy in NPR-B ΔKC transgenic rats 6 weeks after surgery [27]. Although the affinity of CNP to NPRA is much less than to the NPRB receptor [28], and CNP does not increase cGMP accumulation in cells expressing human NPRA [11,29], we cannot finally exclude that transgenic CNP mediates part of its antihypertrophic effect via NPRA. Nevertheless, the combination of data from Langenickel et al and our findings provides clear evidence that the CNP/NPRB axis is implicated in the regulation of cardiomyocyte growth but not in cardiac fibrosis.…”

Natriuretic peptide‐induced cyclic GMP accumulation in adult guinea‐pig cerebellar slices

“…At ANPA receptors, ANP is the most potent for displacing ['25I]-ANP binding, followed by BNP, while CNP is very much less potent. In contrast, CNP appears to be a specific ligand for ANPB receptors (Koller et al, 1991). The third member of the natriuretic peptide family, called the clearance receptor (C-receptor), is dimeric in nature with an unclear physiological role other than the clearance of circulating natriuretic peptides (Levin, 1993).…”

Characterization of natriuretic peptide receptors in the rat parotid

“…Three natriurefic peptide receptors have been identified by molecular cloning, two of these, guanylyl cyclase A (GC-A receptor)(4) and guanylyl cyclase B (GC-B receptor) (5), consisting of a trans-membrane single chain, contain the extracellular ligand binding domain, the cytosolic kinase and guanylyl cyclase catalytic domain, and are capable of synthesizing the second messenger, cGME The other one which does not contain the cytosolic kinase and guanylyl cyclase catalytic domain, has been named the ANP-clearance (AN-P-C) receptor (6). The GC-A receptor binds ANP and BNP with high affinity but has a much lower affinity for CNP, whereas the GC-B receptor has a higher affinity for CNP than for ANP and BNP (7). The ANP-C receptor binds ANP, BNP and CNP with comparable affinity.…”