Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development

Citations Over TimeTop 13% of 2013 papers

Abstract

Organ development is a highly regulated process involving the coordinated proliferation and differentiation of diverse cellular populations. The pathways regulating cell proliferation and their effects on organ growth are complex and for many organs incompletely understood. In all vertebrate species, the cardiac natriuretic peptides (ANP and BNP) are produced by cardiomyocytes in the developing heart. However, their role during cardiogenesis is not defined. Using the embryonic zebrafish and neonatal mammalian cardiomyocytes we explored the natriuretic peptide signaling network during myocardial development. We observed that the cardiac natriuretic peptides ANP and BNP and the guanylate cyclase-linked natriuretic peptide receptors Npr1 and Npr2 are functionally redundant during early cardiovascular development. In addition, we demonstrate that low levels of the natriuretic peptides preferentially activate Npr3, a receptor with Gi activator sequences, and increase cardiomyocyte proliferation through inhibition of adenylate cyclase. Conversely, high concentrations of natriuretic peptides reduce cardiomyocyte proliferation through activation of the particulate guanylate cyclase-linked natriuretic peptide receptors Npr1 and Npr2, and activation of protein kinase G. These data link the cardiac natriuretic peptides in a complex hierarchy modulating cardiomyocyte numbers during development through opposing effects on cardiomyocyte proliferation mediated through distinct cyclic nucleotide signaling pathways.

Related Papers

• → Selective Activation of the B Natriuretic Peptide Receptor by C-Type Natriuretic Peptide (CNP)(1991)730 cited
• → Molecular biology and biochemistry of the natriuretic peptide system(1996)103 cited
• → The natriuretic peptide family(1993)69 cited
• Characterization and functional expression of the natriuretic peptide system in human lens epithelial cells.(2010)
• → Evidence for Atrial Natriuretic Factor Induced Natriuretic Peptide Receptor Subtype Switching in Rat Proximal Tubular Cells during Culture(1998)16 cited