Structural Substrate Conditions Required for Neutral Endopeptidase-Mediated Natriuretic Peptide Degradation

2009 ◽  
Vol 393 (2) ◽  
pp. 496-503 ◽  
Author(s):  
Kristin Pankow ◽  
Anja Schwiebs ◽  
Matthias Becker ◽  
Wolf-Eberhard Siems ◽  
Gerd Krause ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Neutral Endopeptidase ◽  
Peptide Degradation

scholarly journals Vascular actions of brain natriuretic peptide: modulation by atherosclerosis and neutral endopeptidase inhibition

2000 ◽  
Vol 35 (3) ◽  
pp. 796-801 ◽  
Author(s):  
John A Schirger ◽  
J.Aaron Grantham ◽  
Iftikhar J Kullo ◽  
Michihisa Jougasaki ◽  
Paul W Wennberg ◽  
...  
Keyword(s):  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Neutral Endopeptidase

Changes in A-type natriuretic peptide and its receptors induced by a neutral endopeptidase inhibitor in a rat model of sepsis

Surgery Today ◽  
2008 ◽  
Vol 38 (2) ◽  
pp. 130-134 ◽  
Author(s):  
Kanetaka Maeshiro ◽  
Shinzo Takamori ◽  
Hiroharu Mifune ◽  
Toshihiro Matsuo ◽  
Norman Y. Kimura ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Rat Model ◽  
Neutral Endopeptidase

Receptor signaling and neutral endopeptidase are involved in the resistance of C-type natriuretic peptide to human mesangial proliferation and collagen-IV expression

2018 ◽  
Vol 66 (5) ◽  
pp. 1.1-9 ◽  
Author(s):  
Huang Huang Luo ◽  
Cheng Wu ◽  
Peng Hu ◽  
Yang Fang Wu ◽  
Dong Dong Zhang ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Mesangial Cells ◽  
Neutral Endopeptidase ◽  
Collagen Iv ◽  
Guanosine Monophosphate ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Receptor Signaling ◽  
Signal Molecule ◽  
Mesangial Proliferation

C-type natriuretic peptide (CNP) is regarded as a local, paracrine hormone to regulate vascular tone and cell proliferation. Although several in vivo studies have documented that CNP exerts the inhibitory effects on mesangial cells (MCs) proliferation and collagen production, a limited number of studies exist about the resistance of CNP to MCs proliferation in vitro. Besides, whether its receptor signaling and neutral endopeptidase (NEP) are involved remains unclear. In the present study, human MCs were incubated in serum-containing medium in the absence or presence of CNP (0, 10 and 100 pM) for 24, 48 and 72 hours, respectively. CNP administration significantly suppresses MCs proliferation and collagen-IV (Col-IV) expression in a time-dependent and dose-dependent manner. As a down-stream signal molecule of CNP activation, the expressions of natriuretic peptide receptor (NPR)-B, cyclic guanosine monophosphate-dependent protein kinases II and NPR-C were obviously augmented, whereas NEP expression was significantly decreased after CNP treatment. In conclusion, receptor signaling and NEP are involved in the resistance of CNP to human mesangial proliferation and Col-IV expression.

Apparent B-type natriuretic peptide selectivity in the kidney due to differential processing

2001 ◽  
Vol 79 (8) ◽  
pp. 715-722 ◽  
Author(s):  
Ichiro Kishimoto ◽  
F Kent Hamra ◽  
David L Garbers
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Spectroscopic Analysis ◽  
Cultured Cells ◽  
Neutral Endopeptidase ◽  
Differential Processing ◽  
Primary Means ◽  
Specific Degradation ◽  
Atrial Natriuretic

Two natriuretic peptides, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), are found principally in the heart. In preliminary experiments with mouse kidney cells or slices, we found mouse BNP1-45 much more potent than ANP1-28 in causing elevations of cGMP (>50-fold). The guanylyl cyclase-A (GC-A) receptor has been suggested to represent the primary means by which both peptides signal. In cultured cells overexpressing GC-A, BNP and ANP were almost equivalent in potency, suggesting that a receptor unique for BNP exists in the kidney. However, in mice lacking the GC-A gene, neither BNP nor ANP significantly elevated cGMP in kidney slices. Phosphoramidon, a neutral endopeptidase inhibitor, shifted the apparent potency of ANP to values equivalent to that of BNP, suggesting these kidney cell/slices rapidly degrade ANP but not BNP. Mass spectroscopic analysis confirmed that ANP is rapidly cleaved at the first cysteine of the disulfide ring, whereas BNP is particularly stable to such cleavage. Other tissues (heart, aorta) failed to significantly degrade ANP or BNP, and therefore the kidney-specific degradation of ANP provides a mechanism for preferential regulation of kidney function by BNP independent of peripheral ANP concentration.Key words: guanylyl cyclase-A, atrial natriuretic peptide, B-type natriuretic peptide, neutral endopeptidase.

Regional plasma levels of cardiac peptides and their response to acute neutral endopeptidase inhibition in man

1998 ◽  
Vol 95 (5) ◽  
pp. 547-555 ◽  
Author(s):  
J. G. LAINCHBURY ◽  
M. G. NICHOLLS ◽  
E. A. ESPINER ◽  
H. IKRAM ◽  
T. G. YANDLE ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Coronary Sinus ◽  
Femoral Artery ◽  
Natriuretic Peptides ◽  
Plasma Levels ◽  
Neutral Endopeptidase ◽  
Brain Natriuretic Peptides ◽  
Atrial Natriuretic

1.The cardiac natriuretic peptides, atrial natriuretic peptide and brain natriuretic peptide, are degraded via clearance receptors and the enzyme neutral endopeptidase (EC 3.4.24.11). We studied the regional plasma concentrations of these peptides and their response to acute neutral endopeptidase inhibition in a consecutive series of patients with a broad spectrum of severity of cardiac dysfunction who were undergoing diagnostic right and left heart catheterization (24 patients, mean age 62.6 years). 2.Baseline blood samples were obtained for hormone analysis from femoral artery, femoral vein, renal vein, hepatic vein, superior vena cava, coronary sinus and pulmonary artery, and initial haemodynamic measurements were made. Twelve patients then received a neutral endopeptidase inhibitor (SCH 32615, 200 ;mg intravenously) and 12 received vehicle alone. The cardiac catheterization procedure was then completed and haemodynamic and hormone measurements were repeated. 3.Haemodynamic status was similar at baseline in both groups, and at repeated measurement (post-procedure after placebo or active drugs) haemodynamic variables were not significantly different from baseline values. Plasma levels of atrial and brain natriuretic peptides exhibited an arteriovenous increment (344% and 124% respectively) across the heart (femoral artery to coronary sinus) and decrement (by 28–54% and 9–16% respectively) across all other tissue beds (P< 0.05 for all) except the lung (no change). Final levels of atrial natriuretic peptide rose above initial levels at all sites in both groups (P< 0.05) except coronary sinus levels in the vehicle group (no change). The increase was consistently greater in the inhibitor group at all sites (P< 0.05 versus placebo). Levels of brain natriuretic peptide rose at all sites in the inhibitor group only (P< 0.05). The transcardiac step-up in atrial natriuretic peptide was markedly augmented after the administration of neutral endopeptidase inhibitor. Other tissue gradients were not significantly altered by neutral endopeptidase inhibitor. 4.Atrial and brain natriuretic peptides in plasma are degraded by a number of tissues, and respond differently to cardiac catheterization. Neutral endopeptidase has a significant role in determining plasma levels of natriuretic peptides, in part perhaps by influencing the amount of intact peptide reaching the circulation after secretion from the heart.

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