735 Role of P38 MAPK in aldosterone-induced glomerular injury in natriuretic peptide receptor-A deficient mice

2012 ◽  
Vol 30 (Supplement 1) ◽  
pp. e213
Author(s):  
Yukiko Kato ◽  
Masashi Mukoyama ◽  
Hideki Yokoi ◽  
Yoshihisa Ogawa ◽  
Kiyoshi Mori ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Natriuretic Peptide ◽  
Natriuretic Peptide Receptor ◽  
Glomerular Injury ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A ◽  
Deficient Mice

scholarly journals The Importance of Natriuretic Peptides in Cardiometabolic Diseases

2020 ◽  
Vol 4 (6) ◽  
Author(s):  
Shravya Vinnakota ◽  
Horng H Chen
Keyword(s):  
Heart Failure ◽  
Natriuretic Peptide ◽  
Defense Mechanisms ◽  
Pressure Overload ◽  
Natriuretic Peptide Receptor ◽  
Therapeutic Role ◽  
Peptide Receptor ◽  
Genes Encoding ◽  
Natriuretic Peptide Receptor A

Abstract The natriuretic peptide (NP) system is composed of 3 distinct peptides (atrial natriuretic peptide or ANP, B-type natriuretic peptide or BNP, and C-type natriuretic peptide or CNP) and 3 receptors (natriuretic peptide receptor-A or NPR-A or particulate guanynyl cyclase-A natriuretic peptide receptor-B or NPR-B or particulate guanynyl cyclase-B, and natriuretic peptide receptor-C or NPR-C or clearance receptor). ANP and BNP function as defense mechanisms against ventricular stress and the deleterious effects of volume and pressure overload on the heart. Although the role of NPs in cardiovascular homeostasis has been extensively studied and well established, much remains uncertain about the signaling pathways in pathological states like heart failure, a state of impaired natriuretic peptide function. Elevated levels of ANP and BNP in heart failure correlate with disease severity and have a prognostic value. Synthetic ANP and BNP have been studied for their therapeutic role in hypertension and heart failure, and promising trials are under way. In recent years, the expression of ANP and BNP in human adipocytes has come to light. Through their role in promotion of adipocyte browning, lipolysis, lipid oxidation, and modulation of adipokine secretion, they have emerged as key regulators of energy consumption and metabolism. NPR-A signaling in skeletal muscles and adipocytes is emerging as pivotal to the maintenance of long-term insulin sensitivity, which is disrupted in obesity and reduced glucose-tolerance states. Genetic variants in the genes encoding for ANP and BNP have been associated with a favorable cardiometabolic profile. In this review, we discuss several pathways that have been proposed to explain the role of NPs as endocrine networkers. There is much to be explored about the therapeutic role of NPs in improving metabolic milieu.

The role of natriuretic peptide receptor-A signaling in unilateral lung ischemia-reperfusion injury in the intact mouse

2008 ◽  
Vol 294 (4) ◽  
pp. L714-L723 ◽  
Author(s):  
Jeffrey M. Dodd-o ◽  
Maria L. Hristopoulos ◽  
Kathleen Kibler ◽  
Jolanta Gutkowska ◽  
Suhayla Mukaddam-Daher ◽  
...  
Keyword(s):  
Lung Injury ◽  
Natriuretic Peptide ◽  
Ischemia Reperfusion ◽  
Intracellular Camp ◽  
Natriuretic Peptide Receptor ◽  
Intact Mouse ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A

Ischemia-reperfusion (IR) causes human lung injury in association with the release of atrial and brain natriuretic peptides (ANP and BNP), but the role of ANP/BNP in IR lung injury is unknown. ANP and BNP bind to natriuretic peptide receptor-A (NPR-A) generating cGMP and to NPR-C, a clearance receptor that can decrease intracellular cAMP. To determine the role of NPR-A signaling in IR lung injury, we administered the NPR-A blocker anantin in an in vivo SWR mouse preparation of unilateral lung IR. With uninterrupted ventilation, the left pulmonary artery was occluded for 30 min and then reperfused for 60 or 150 min. Anantin administration decreased IR-induced Evans blue dye extravasation and wet weight in the reperfused left lung, suggesting an injurious role for NPR-A signaling in lung IR. In isolated mouse lungs, exogenous ANP (2.5 nM) added to the perfusate significantly increased the filtration coefficient sevenfold only if lungs were subjected to IR. This effect of ANP was also blocked by anantin. Unilateral in vivo IR increased endogenous plasma ANP, lung cGMP concentration, and lung protein kinase G (PKGI) activation. Anantin enhanced plasma ANP concentrations and attenuated the increase in cGMP and PKGI activation but had no effect on lung cAMP. These data suggest that lung IR triggered ANP release and altered endothelial signaling so that NPR-A activation caused increased pulmonary endothelial permeability.

scholarly journals Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A–deficient mice

2001 ◽  
Vol 107 (8) ◽  
pp. 975-984 ◽  
Author(s):  
Joshua W. Knowles ◽  
Giovanni Esposito ◽  
Lan Mao ◽  
John R. Hagaman ◽  
Jennifer E. Fox ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A ◽  
Pressure Independent ◽  
Deficient Mice

Role of cyclic GMP and calcineurin in homologous and heterologous desensitization of natriuretic peptide receptor-A

2006 ◽  
Vol 84 (5) ◽  
pp. 539-546 ◽  
Author(s):  
Yann Fortin ◽  
André De Léan
Keyword(s):  
Natriuretic Peptide ◽  
Present Report ◽  
Calcineurin Inhibitors ◽  
Cytosolic Calcium ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Heterologous Desensitization ◽  
Natriuretic Peptide Receptor A ◽  
Homologous Desensitization

The natriuretic peptide receptor-A (NPR-A) mediates natriuretic, hypotensive, and antihypertrophic effects of natriuretic peptides through the production of cGMP. In pathological conditions such as heart failure, these effects are attenuated by homologous and heterologous desensitization mechanisms resulting in the dephosphorylation of the cytosolic portion of the receptor. In contrast with natriuretic peptide-induced desensitization, pressor hormone-induced desensitization is dependent on protein kinase C (PKC) stimulation and (or) cytosolic calcium elevation. Mechanisms by which PKC and Ca2+ promote NPR-A desensitization are not known. The role of cGMP and of the cytosolic Ca2+ pathways in NPR-A desensitization were therefore studied. In contrast with the activation of NPR-A by its agonist, activation of soluble guanylyl cyclases of LLC-PK1 cells by sodium nitroprusside also leads to a production of cGMP but without altering NPR-A activation. Consequently, cGMP elevation per se does not appear to mediate homologous desensitization of NPR-A. In addition, cytosolic calcium increase is required only for the heterologous desensitization pathway since the calcium chelator BAPTA-AM blocks only PMA or ionomycin-induced desensitization. Calcineurin inhibitors block the NPR-A guanylyl cyclase heterologous desensitization induced by ionomycin, suggesting an essential role for this Ca2+-stimulated phosphatase in NPR-A desensitization. In summary, the present report demonstrates that neither cGMP nor Ca2+ cytosolic elevation cause NPR-A homologous desensitization. Our results also indicate for the first time a role for calcineurin in NPR-A heterologous desensitization.

scholarly journals Role of FQQI motif in the internalization, trafficking, and signaling of guanylyl-cyclase/natriuretic peptide receptor-A in cultured murine mesangial cells

2016 ◽  
Vol 310 (1) ◽  
pp. F68-F84 ◽  
Author(s):  
Indra Mani ◽  
Renu Garg ◽  
Kailash N. Pandey
Keyword(s):  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Mesangial Cells ◽  
Adaptor Protein ◽  
Target Cells ◽  
Natriuretic Peptide Receptor ◽  
Subcellular Trafficking ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A

Binding of the cardiac hormone atrial natriuretic peptide (ANP) to transmembrane guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), produces the intracellular second messenger cGMP in target cells. To delineate the critical role of an endocytic signal in intracellular sorting of the receptor, we have identified a FQQI (Phe790, Gln791, Gln792, and Ile793) motif in the carboxyl-terminal region of NPRA. Mouse mesangial cells (MMCs) were transiently transfected with the enhanced green fluorescence protein (eGFP)-tagged wild-type (WT) and mutant constructs of eGFP-NPRA. The mutation FQQI/AAAA, in the eGFP-NPRA cDNA sequence, markedly attenuated the internalization of mutant receptors by almost 49% compared with the WT receptor. Interestingly, we show that the μ1B subunit of adaptor protein-1 binds directly to a phenylalanine-based FQQI motif in the cytoplasmic tail of the receptor. However, subcellular trafficking indicated that immunofluorescence colocalization of the mutated receptor with early endosome antigen-1 (EEA-1), lysosome-associated membrane protein-1 (LAMP-1), and Rab 11 marker was decreased by 57% in early endosomes, 48% in lysosomes, and 42% in recycling endosomes, respectively, compared with the WT receptor in MMCs. The receptor containing the mutated motif (FQQI/AAAA) also produced a significantly decreased level of intracellular cGMP during subcellular trafficking than the WT receptor. The coimmunoprecipitation assay confirmed a decreased level of colocalization of the mutant receptor with subcellular compartments during endocytic processes. The results suggest that the FQQI motif is essential for the internalization and subcellular trafficking of NPRA during the hormone signaling process in intact MMCs.

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