Correlation between the compact regions predicted by the Average Distance Map (ADM) and the biologically active sites in atrial natriuretic peptide

1992 ◽  
Vol 11 (5) ◽  
pp. 579-581 ◽  
Author(s):  
Takeshi Kikuchi
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Active Sites ◽  
Average Distance ◽  
Biologically Active ◽  
Distance Map ◽  
Average Distance Map ◽  
Atrial Natriuretic

Atrial natriuretic peptide inhibits cell cycle activity of embryonic cardiac progenitor cells via its NPRA receptor signaling axis

2015 ◽  
Vol 308 (7) ◽  
pp. C557-C569 ◽  
Author(s):  
Adam Hotchkiss ◽  
Tiam Feridooni ◽  
Mark Baguma-Nibasheka ◽  
Kathleen McNeil ◽  
Sarita Chinni ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Progenitor Cells ◽  
Natriuretic Peptide ◽  
Biological Effects ◽  
Active Form ◽  
Specific Inhibitor ◽  
Ventricular Myocardium ◽  
Biologically Active ◽  
Cardiac Progenitor Cells ◽  
Atrial Natriuretic

The biological effects of atrial natriuretic peptide (ANP) are mediated by natriuretic peptide receptors (NPRs), which can either activate guanylyl cyclase (NPRA and NPRB) or inhibit adenylyl cyclase (NPRC) to modulate intracellular cGMP or cAMP, respectively. During cardiac development, ANP serves as an early maker of differentiating atrial and ventricular chamber myocardium. As development proceeds, expression of ANP persists in the atria but declines in the ventricles. Currently, it is not known whether ANP is secreted or the ANP-NPR signaling system plays any active role in the developing ventricles. Thus the primary aims of this study were to 1) examine biological activity of ANP signaling systems in embryonic ventricular myocardium, and 2) determine whether ANP signaling modulates proliferation/differentiation of undifferentiated cardiac progenitor cells (CPCs) and/or cardiomyocytes. Here, we provide evidence that ANP synthesized in embryonic day (E)11.5 ventricular myocytes is actively secreted and processed to its biologically active form. Notably, NPRA and NPRC were detected in E11.5 ventricles and exogenous ANP stimulated production of cGMP in ventricular cell cultures. Furthermore, we showed that exogenous ANP significantly decreased cell number and DNA synthesis of CPCs but not cardiomyocytes and this effect could be reversed by pretreatment with the NPRA receptor-specific inhibitor A71915. ANP treatment also led to a robust increase in nuclear p27 levels in CPCs compared with cardiomyocytes. Collectively, these data provide evidence that in the developing mammalian ventricles ANP plays a local paracrine role in regulating the balance between CPC proliferation and differentiation via NPRA/cGMP-mediated signaling pathways.

scholarly journals Expression and secretion of biologically active human atrial natriuretic peptide in Saccharomyces cerevisiae.

1986 ◽  
Vol 261 (11) ◽  
pp. 4789-4796
Author(s):  
G P Vlasuk ◽  
G H Bencen ◽  
R M Scarborough ◽  
P K Tsai ◽  
J L Whang ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Biologically Active ◽  
Human Atrial Natriuretic Peptide ◽  
Atrial Natriuretic

scholarly journals Regulation of platelet clearance receptors for atrial natriuretic peptide in diabetic nephropathy.

1992 ◽  
Vol 3 (2) ◽  
pp. 236-243
Author(s):  
S Canaan-Kuhl ◽  
L Parra-Roide ◽  
J W Bialek ◽  
R L Jamison ◽  
B D Myers
Keyword(s):  
Diabetic Nephropathy ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Biologically Active ◽  
Scatchard Analysis ◽  
Down Regulation ◽  
Anp Receptors ◽  
Circulating Levels ◽  
Dissociation Constant Kd ◽  
Atrial Natriuretic

The findings that circulating levels of atrial natriuretic peptide (ANP) are elevated in diabetic nephropathy and that the magnitude of the urinary excretion rate of cGMP in response to hypervolemia-induced ANP release is blunted have recently been reported. The purpose of this study was to determine whether these abnormalities are associated with the down-regulation of ANP receptors. Because biologically active (A) ANP receptors in the kidney are inaccessible, we have examined the binding of (125I alpha)ANP to clearance (C) receptors on platelets obtained from patients with diabetic nephropathy. Scatchard analysis revealed a reduction in such binding sites compared with those in healthy controls: 12 +/- 2 versus 19 +/- 2 per platelet, respectively (P less than 0.001). The dissociation constant, Kd, was higher: 66.7 +/- 33.1 versus 38.5 +/- 11 pM, respectively (P less than 0.02). The reduced number of receptors could reflect the down-regulation of ANP C receptors in response to an elevation of plasma levels of ANP, the median value of which was 10.6 versus 7.1 pmol/L in controls (P less than 0.05). Alternatively, the findings could represent a primary adaptation by C receptors to elevate plasma ANP levels and increase the availability of the peptide to biologically active renal receptors. The latter adaptation would serve to mitigate the sodium retention that attends diabetic nephropathy.

Role of cardiac innervation in atrial natriuretic peptide secretion in transplanted heart recipients

1993 ◽  
Vol 265 (1) ◽  
pp. F112-F118
Author(s):  
B. Geny ◽  
F. Piquard ◽  
M. Follenius ◽  
B. Mettauer ◽  
A. Schaefer ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Arginine Vasopressin ◽  
Volume Expansion ◽  
Biologically Active ◽  
Control Group ◽  
Cardiac Innervation ◽  
Total Blood ◽  
Atrial Natriuretic

To investigate whether cardiac innervation modulates atrial natriuretic peptide (ANP) secretion, we performed acute volume expansion on eight normal and eight matched (age, weight, and total blood volume) transplanted denervated heart patients (Htx), while monitoring fluid-regulating hormone, systemic blood pressure, and echocardiographic atrial area changes. At rest, plasma ANP and guanosine 3',5'-cyclic monophosphate (cGMP) were lower in control subjects than in Htx (45 +/- 16 vs. 103 +/- 35 pg/l and 0.9 +/- 0.3 vs. 3.5 +/- 1.4 pM, respectively; P < 0.001). Plasma active renin, aldosterone, and catecholamines did not differ significantly in the two populations, whereas arginine vasopressin and cortisol were higher in controls (P < 0.01 and P < 0.005). Although volume expansion (+15%) and atrial stretch were similar in the two groups, plasma ANP and cGMP increased significantly only in the Htx group (103 +/- 35 to 189 +/- 69 pg/l and 3.5 +/- 1.4 to 5.8 +/- 1.4 pM, respectively; P < 0.001). The decrease observed for the other hormones was not significant except for arginine vasopressin and cortisol (P < 0.05 and P < 0.001) in the control group. These results support the hypothesis of an inhibitory role of cardiac innervation in biologically active ANP secretion in humans, at rest and after acute volume expansion.

scholarly journals Functional Screening Identifies MicroRNA Regulators of Corin Activity and Atrial Natriuretic Peptide Biogenesis

2019 ◽  
Vol 39 (23) ◽  
Author(s):  
Selvi Celik ◽  
Mardjaneh Karbalaei-Sadegh ◽  
Göran Rådegran ◽  
J. Gustav Smith ◽  
Olof Gidlöf
Keyword(s):  
Gene Expression ◽  
Atrial Natriuretic Peptide ◽  
Serine Protease ◽  
Natriuretic Peptide ◽  
Active Form ◽  
Biologically Active ◽  
Functional Screening ◽  
Human Cardiomyocytes ◽  
Gene And Protein Expression ◽  
Atrial Natriuretic

ABSTRACT Atrial natriuretic peptide (ANP) represents an attractive therapeutic target in hypertension and heart failure. The biologically active form of ANP is produced by the cardiac serine protease corin, and modulation of its activity might therefore represent a novel approach for ANP augmentation. MicroRNAs (miRNAs) are pervasive regulators of gene expression, but their potential role in regulating corin activity has not been elucidated. Our aim was to systematically identify and characterize miRNA regulators of corin activity in human cardiomyocytes. An assay for measuring serine protease activity in human induced pluripotent stem cell (iPS)-derived cardiomyocytes was used to perform a comprehensive screening of miRNA family inhibitors (n = 42). miRNA 1-3p (miR-1-3p) was identified as a potent inhibitor of corin activity. The interaction between miR-1-3p and a specific target site in the CORIN 3′ untranslated region (3′ UTR) was confirmed through argonaute 2 (AGO2)-RNA immunoprecipitation and reporter assays. Inhibition of miR-1-3p resulted in upregulation of CORIN gene and protein expression, as well as a concomitant increase in extracellular ANP. Additionally, miR-1-3p was found to interact with and inhibit the expression of several transcriptional activators of ANP gene expression. In conclusion, we have identified a novel regulator of corin activity and ANP biogenesis in human cardiomyocytes that might be of potential future therapeutic utility.

Corin, a Transmembrane Cardiac Serine Protease, as a Pro-Atrial Natriuretic Peptide Convertase

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 709-710
Author(s):  
Wei Yan ◽  
Faye Wu ◽  
John Morser ◽  
Qingyu Wu
Keyword(s):  
Blood Pressure ◽  
Atrial Natriuretic Peptide ◽  
Serine Protease ◽  
Natriuretic Peptide ◽  
Transmembrane Protein ◽  
Biologically Active ◽  
Expression Vectors ◽  
Sequence Specificity ◽  
293 Cells ◽  
Atrial Natriuretic

P92 Atrial natriuretic peptide (ANP) is a cardiac hormone that reduces high blood pressure by promoting salt excretion, decreasing blood volume and relaxing vessel tension. It is implicated in major cardiovascular diseases such as hypertension and congestive heart failure. In cardiomyocytes, ANP is synthesized as a precursor, pro-ANP, that is converted to biologically active ANP by an unknown membrane-associated serine protease. Recently, we cloned a novel cardiac serine protease, corin, that has the predicted structure of a type II transmembrane protein. Northern and in situ hybridization detected corin mRNA in the heart where its expression was most abundant in cardiomyocytes of the atrium. Corin mRNA was also detected in developing kidney and bones. The overall expression pattern of corin mRNA was very similar to that of ANP, leading to our hypothesis that corin is the pro-ANP convertase. To test this hypothesis, we constructed expression vectors for both human corin and pro-ANP. Recombinant corin and pro-ANP were expressed in human 293 cells. Effects of corin on pro-ANP processing was examined by western analysis. The results showed that human corin, but not control proteases prothrombin and hepsin, converted pro-ANP to ANP in the cell-based experiments. To determine sequence specificity of corin-mediated cleavage in pro-ANP, we constructed a mutant pro-ANP R98G in which the predicted cleave site residue Arg98 was replaced with a Gly. In co-transfection experiments, corin processed wild-type pro-ANP but not mutant pro-ANP R98G, indicating that corin-mediated cleavage in pro-ANP is highly sequence specific. We also examined effects of protease inhibitors on processing of pro-ANP by corin. Our results showed that the activity of corin was inhibited by aprotinin, benzamidine and leupeptin but not soybean trypsin inhibitor. Similar effects of these proteases on pro-ANP processing were reported previously. Thus, corin matches all known characteristics of the long-sought pro-ANP convertase. Identification of corin as the pro-ANP convertase suggests a new regulatory mechanism for the ANP-mediated pathway that is important for controlling blood pressure.

Atrial natriuretic peptide does not alter cerebrospinal fluid formation in sheep

1992 ◽  
Vol 262 (5) ◽  
pp. R860-R864 ◽  
Author(s):  
A. Chodobski ◽  
J. Szmydynger-Chodobska ◽  
E. Cooper ◽  
M. J. McKinley
Keyword(s):  
Cerebrospinal Fluid ◽  
Atrial Natriuretic Peptide ◽  
Choroid Plexus ◽  
Natriuretic Peptide ◽  
Formation Rate ◽  
Biologically Active ◽  
Dilution Method ◽  
Time Control ◽  
Csf Formation Rate ◽  
Atrial Natriuretic

Because the choroid plexus has been shown to have a high density of atrial natriuretic peptide (ANP) binding sites, we investigated the effect of intracerebroventricular and intravenous administrations of ANP on cerebrospinal fluid (CSF) formation. CSF formation rate was measured in conscious sheep with a dye-dilution method using blue dextran 2000 as an indicator substance. During the experiment animals were partially restrained in a sling, and their ventricular systems were perfused with artificial CSF containing the indicator substance. ANP (alpha-human ANP) administered centrally at rates of 0.015-15 ng/min, resulting in CSF ANP concentrations ranging from physiological to pharmacological CSF hormone levels, was found not to influence CSF formation. Similarly, intravenous administration of ANP at a rate of 10 ng.kg-1.min-1 did not affect CSF formation, i.e., decreases in CSF formation rate in all experiments involving ANP administration were not significantly different from those observed in time control experiments. Our results suggest that ANP does not significantly affect CSF production in sheep. It is possible that the lack of effect of ANP on CSF formation is associated with the predominance in the choroid plexus of clearance receptors over biologically active receptors.

Localization and in vitro actions of atrial natriuretic peptide in the cat carotid body

1991 ◽  
Vol 70 (2) ◽  
pp. 942-946 ◽  
Author(s):  
Z. Z. Wang ◽  
L. He ◽  
L. J. Stensaas ◽  
B. G. Dinger ◽  
S. J. Fidone
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Carotid Body ◽  
Sodium Intake ◽  
Volume Overload ◽  
Systemic Blood Pressure ◽  
Biologically Active ◽  
Type I ◽  
Atrial Natriuretic

Previous studies of atrial natriuretic peptide (ANP) have indicated that its release from the heart and from discrete areas of the central nervous system evokes coordinated physiological and behavioral adjustments that mitigate the adverse hypertensive effects of volume overload and/or acute increases in sodium intake. Because the reflex activity initiated by arterial chemoreceptors of the carotid body directly contributes to the integrated regulation of systemic blood pressure, we have investigated the possibility that ANP has a significant role in the chemosensory process as well. Our immunocytochemical studies show that ANP-like immunoreactivity is present in the preneural chemosensitive type I cells in the cat carotid body. Furthermore we found that the biologically active ANP fragment atriopeptin III is a potent inhibitor of carotid sinus nerve activity evoked by hypoxia. Our findings suggest that circulating and/or endogenous ANP may modulate carotid body function as part of a coordinated response to changes in systemic volume and solute balance.

scholarly journals Role of Glycosylation in Corin Zymogen Activation

2007 ◽  
Vol 282 (38) ◽  
pp. 27728-27735 ◽  
Author(s):  
Xudong Liao ◽  
Wei Wang ◽  
Shenghan Chen ◽  
Qingyu Wu
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Cysteine Proteases ◽  
Biologically Active ◽  
Zymogen Activation ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
Neonatal Cardiomyocytes ◽  
293 Cells ◽  
Atrial Natriuretic

The cardiac serine protease corin is the pro-atrial natriuretic peptide convertase. Corin is made as a zymogen, which is activated by proteolytic cleavage. Previous studies showed that recombinant human corin expressed in HEK 293 cells was biologically active, but activated corin fragments were not detectable, making it difficult to study corin activation. In this study, we showed that recombinant rat corin was activated in HEK 293 cells, murine HL-1 cardiomyocytes, and rat neonatal cardiomyocytes. In these cells, activated corin represented a small fraction of the total corin molecules. The activation of recombinant rat corin was inhibited by small molecule trypsin inhibitors but not inhibitors for matrix metalloproteinases or cysteine proteases, suggesting that a trypsin-like protease activated corin in these cells. Glycosidase digestion showed that rat and human corin proteins contained substantial N-glycans but little O-glycans. Treatment of HEK 293 cells expressing rat corin with tunicamycin prevented corin activation and inhibited its pro-atrial natriuretic peptide processing activity. Similar effects of tunicamycin on endogenous corin activity were found in HL-1 cells. Mutations altering the two N-glycosylation sites in the protease domain of rat corin prevented its activation in HEK 293 and HL-1 cells. Our results indicate that N-linked oligosaccharides play an important role in corin activation.

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