Stimulation of atrial natriuretic peptide release by neurokinins in neonatal rat ventricular cardiomyocytes

1996 ◽  
Vol 270 (3) ◽  
pp. H935-H944 ◽  
Author(s):  
D. J. Church ◽  
S. J. Arkinstall ◽  
M. B. Vallotton ◽  
A. Chollet ◽  
E. Kawashima ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Cultured Cells ◽  
Neonatal Rat ◽  
Receptor Subtypes ◽  
Camp Production ◽  
Ventricular Cardiomyocytes ◽  
Nk3 Receptor ◽  
Prostaglandin Antagonists ◽  
Atrial Natriuretic

The effect of substance P (SP) on atrial natriuretic peptide (ANP) release was studied in neonatal rat ventricular cardiomyocytes. Incubation of cells with SP led to a marked increase in ANP secretion, a response accompanied by increases in alpha-type protein kinase C (PKC) in the membranous cell fraction and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) formation and a small increase in adenosine 3',5'-cyclic monophosphate (cAMP) production. A role for PKC in SP-induced 6-keto-PGF1 alpha formation and ANP release was apparent insofar as the responses were suppressed by PKC inhibitors and in PKC-downregulated cells. Furthermore, SP-induced 6-keto-PGF1 alpha production was strongly correlated with SP-induced ANP secretion (r = 0.91, P < 0.0001, n = 27), suggesting a role for prostaglandins in SP-mediated ANP release. Supporting this, indomethacin abolished SP-induced ANP release, whereas PGE2, PGF2 alpha, and prostacyclin (PGI2) promoted ANP secretion in this system. Both the profile of SP-induced cAMP production and results obtained with prostaglandin antagonists suggest that a prostanoid FP receptor is at the basis of this response. Finally, both neurokinins A and B induced similar ANP responses, whereas cultured cells were found to contain mRNA transcripts coding for both neurokinin NK1 and NK3 receptor subtypes. Overall, these results suggest that SP induces ANP secretion in neonatal ventricular cardiomyocytes through a PKC- and prostaglandin-dependent signaling pathway.

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.

Lack of effect of atrial natriuretic peptide and urodilatin on vasopressin-stimulated cyclic AMP production in microdissected rat inner medullary collecting ducts

1994 ◽  
Vol 12 (2) ◽  
pp. 149-154
Author(s):  
W J Burgess ◽  
M N Perrott ◽  
R J Balment
Keyword(s):  
Cyclic Amp ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Absolute Magnitude ◽  
Camp Production ◽  
Collecting Ducts ◽  
Medullary Collecting Duct ◽  
Atrial Natriuretic

ABSTRACT It is unclear whether the diuretic effects of atrial natriuretic peptide (ANP) result, in part, from an inhibition of the renal actions of vasopressin. Moreover, accruing evidence suggests that the kidneys themselves may produce an ANP-like peptide, urodilatin, which shares many of the renal actions of ANP. The mechanism underlying the diuretic action of urodilatin has not yet been examined. Accordingly, we have investigated the potential modulatory actions of both ANP and urodilatin on vasopressin-stimulated cyclic AMP (cAMP) production in microdissected inner medullary collecting duct (IMCD) segments of rat kidney. ANP and urodilatin alone (at 10−8 or 10−6 m) had no demonstrable effect on cAMP accumulation in IMCD segments. Moreover, neither ANP nor urodilatin (each at 10−6 m) significantly altered either the profile or the absolute magnitude of the cAMP response stimulated by vasopressin. These findings indicate that neither ANP nor urodilatin interacts with the vasopressin-sensitive adenylate cyclase site in the rat IMCD to contribute to its diuretic actions.

Endothelin increases the synthesis and secretion of atrial natriuretic peptide in neonatal rat cardiocytes

1991 ◽  
Vol 261 (2) ◽  
pp. E177-E182 ◽  
Author(s):  
D. G. Gardner ◽  
E. D. Newman ◽  
K. K. Nakamura ◽  
K. P. Nguyen
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Primary Cultures ◽  
Secretory Activity ◽  
Neonatal Rat ◽  
Regulatory Function ◽  
Mrna Accumulation ◽  
Calmodulin Antagonist ◽  
Natriuretic Hormone ◽  
Atrial Natriuretic

Endothelin (ET) effected a dose-dependent increment in atrial natriuretic peptide (ANP) secretion and ANP mRNA accumulation in neonatal rat atrial and ventricular cardiocytes but had no effect on the processing of the ANP prohormone to the mature ANP product. The secretagogue effect was not limited by cell density. Both basal and ET-dependent secretory activity were abrogated by the calmodulin antagonist calmidazolium but were unaffected by meclophenamate or pertussis toxin. The magnitude of the ET-dependent increment in ANP secretion was amplified by culturing the cells in a dynamically pulsating (vs. static) environment, implying an interaction between mechanical and agonist-mediated secretory stimuli in this system. ET also promoted immunoreactive ANP release from primary cultures of fetal rat hypothalamic cultures, suggesting that this regulatory function may be generally employed in ANP gene-expressing cells. These findings demonstrate that ET has parallel effects on ANP synthesis and secretion and support a role for this peptide in the regulation of local and circulating levels of the natriuretic hormone.

scholarly journals Divergent regulation of the human atrial natriuretic peptide gene by c-jun and c-fos.

1992 ◽  
Vol 12 (1) ◽  
pp. 292-301 ◽  
Author(s):  
B Kovacic-Milivojević ◽  
D G Gardner
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Transcriptional Activation ◽  
Gene Promoter ◽  
Regulatory Elements ◽  
Neonatal Rat ◽  
Regulatory Sequence ◽  
Mobility Shift ◽  
Human Atrial Natriuretic Peptide ◽  
Atrial Natriuretic

Employing transient transfection analysis in neonatal rat cardiocytes, we have demonstrated that overexpression of c-jun results in a dose-dependent induction of the human atrial natriuretic peptide (hANP) gene promoter. Studies using a series of mutations in the hANP gene promoter identified a TRE-like, cis-acting regulatory sequence which conferred c-jun sensitivity. This same region was shown to interact with the c-jun/c-fos complex in an in vitro gel mobility shift assay. Selective mutation of this site suppressed basal activity of the hANP promoter and significantly reduced c-jun-dependent activation. Overexpression of c-fos had a biphasic effect on hANP gene promoter activity. At low levels, in concert with c-jun, it activated, while at higher levels it suppressed, transcription from the hANP gene promoter. This inhibition was both cell and promoter specific. hANP gene promoter sequences which mediate c-fos-dependent inhibition appear to be separable from those responsible for the induction. In addition, the protein domains on c-fos responsible for transcriptional activation and repression can be segregated topographically, with the inhibitory activity being localized to the carboxy-terminal domain. Thus, c-fos can activate or repress hANP gene expression through two separate functional domains that act on distinct regulatory elements in the hANP gene promoter. These data imply that the ANP gene may be a physiological target for c-fos- and c-jun-dependent activity in the heart and suggest a potential mechanism linking environmental stimuli to its expression.

Myocardial production of prostaglandins: its role in atrial natriuretic peptide release

1995 ◽  
Vol 133 (2) ◽  
pp. 255-259 ◽  
Author(s):  
Chafik Azizi ◽  
Christiane Barthélemy ◽  
Françoise Masson ◽  
Geneviéve Maistre ◽  
Joëlle Eurin ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Significant Rise ◽  
Cyclooxygenase Inhibitor ◽  
Camp Production ◽  
Camp Concentration ◽  
Peptide Release ◽  
Activation Pathways ◽  
Camp Formation ◽  
Atrial Natriuretic

Azizi C, Barthélemy C, Masson F, Maistre G, Eurin J, Carayon A. Myocardial production of prostaglandins: its role in atrial natriuretic peptide release. Eur J Endocrinol 1995;133:255–9. ISSN 0804–4643 In recent years, considerable evidence has been accumulated on prostaglandins (PG) in modulating atrial natriuretic peptide (ANP) release. In the current study we investigated whether eicosanoids promote isoproterenol-induced ANP secretion from superfused rabbit sliced atria. Inclusion of the cyclooxygenase inhibitor indomethacin (10 μmol to the superfusing medium abolished isoproterenol-induced ANP release. Next, PGE2, but not PGF2α or PGI2 (10 μmol), increased ANP release. Furthermore, isoproterenol-induced PGE2 formation was fully attenuated by indomethacin. Dibutyl-cAMP (0.5 mmol) had no effect on PGE2 formation, and the protein kinase A (PKA) inhibitor H89 (20 μmol) did not alter isoproterenol-induced PGE2 formation. On the other hand, indomethacin led to a significant decrease in isoprotrenol-induced cAMP production. In addition, PGE2 enhanced basal cAMP concentration in superfusates. Superfusion of sliced atria by forskolin (10 μmol) or by dibutylcAMP (0.5 mmol) produced a significant rise in ANP release. Finally, H89 was ineffective on basal ANP release but abolished the increase of ANP release in response to isoproterenol or to PGE2. We conclude that: the effect of isoproterenol on ANP release is sensitive to indomethacin and H89; PGE2, but not PGF2α or PGI2, increases ANP release; isoproterenol promotes myocardial PGE2 formation independently of adenylate cyclase and PKA activation pathways; and PGE2-induced ANP release is mediated by cAMP production and subsequent PKA activation. These results suggest that isoproterenol-induced ANP release appears to be mediated at least partly by PGE2 with underlying cAMP formation and PKA activation. C Azizi, Service de Biochimie, CHU Pitié-Salpêtrère, 91 boulevard de l'hôpital, 75634 Paris Cedex 13, France

PDE2-mediated cAMP hydrolysis accelerates cardiac fibroblast to myofibroblast conversion and is antagonized by exogenous activation of cGMP signaling pathways

2014 ◽  
Vol 306 (8) ◽  
pp. H1246-H1252 ◽  
Author(s):  
C. Vettel ◽  
S. Lämmle ◽  
S. Ewens ◽  
C. Cervirgen ◽  
J. Emons ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Sodium Nitroprusside ◽  
Natriuretic Peptide ◽  
Neonatal Rat ◽  
Nitric Oxide Donor ◽  
Signal Molecules ◽  
Protective Mechanism ◽  
Camp Hydrolysis ◽  
Camp And Cgmp ◽  
Atrial Natriuretic

Recent studies suggest that the signal molecules cAMP and cGMP have antifibrotic effects by negatively regulating pathways associated with fibroblast to myofibroblast (MyoCF) conversion. The phosphodiesterase 2 (PDE2) has the unique property to be stimulated by cGMP, which leads to a remarkable increase in cAMP hydrolysis and thus mediates a negative cross-talk between both pathways. PDE2 has been recently investigated in cardiomyocytes; here we specifically addressed its role in fibroblast conversion and cardiac fibrosis. PDE2 is abundantly expressed in both neonatal rat cardiac fibroblasts (CFs) and cardiomyocytes. The overexpression of PDE2 in CFs strongly reduced basal and isoprenaline-induced cAMP synthesis, and this decrease was sufficient to induce MyoCF conversion even in the absence of exogenous profibrotic stimuli. Functional stress-strain experiments with fibroblast-derived engineered connective tissue (ECT) demonstrated higher stiffness in ECTs overexpressing PDE2. In regard to cGMP, neither basal nor atrial natriuretic peptide-induced cGMP levels were affected by PDE2, whereas the response to nitric oxide donor sodium nitroprusside was slightly but significantly reduced. Interestingly, despite persistently depressed cAMP levels, both cGMP-elevating stimuli were able to completely prevent the PDE2-induced MyoCF phenotype, arguing for a double-tracked mechanism. In conclusion, PDE2 accelerates CF to MyoCF conversion, which leads to greater stiffness in ECTs. Atrial natriuretic peptide- and sodium nitroprusside-mediated cGMP synthesis completely reverses PDE2-induced fibroblast conversion. Thus PDE2 may augment cardiac remodeling, but this effect can also be overcome by enhanced cGMP. The redundant role of cAMP and cGMP as antifibrotic meditators may be viewed as a protective mechanism in heart failure.

Atrial natriuretic peptide gene expression and its secretion by pneumocytes derived from neonatal rat lungs

1988 ◽  
Vol 156 (2) ◽  
pp. 619-627 ◽  
Author(s):  
Hiroaki Matsubara ◽  
Yasukiyo Mori ◽  
Yukihisa Umeda ◽  
Shinzo Oikawa ◽  
Hiroshi Nakazato ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Neonatal Rat ◽  
Rat Lungs ◽  
Peptide Gene ◽  
Atrial Natriuretic

scholarly journals Prolonged Atrial Natriuretic Peptide Exposure Stimulates Guanylyl Cyclase-A Degradation

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2769-2776 ◽  
Author(s):  
Darcy R. Flora ◽  
Lincoln R. Potter
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Cultured Cells ◽  
Volume Overload ◽  
Receptor Expression ◽  
Dependent Manner ◽  
Down Regulation ◽  
Time Required ◽  
Atrial Natriuretic

Natriuretic peptide receptor-A (NPR-A), also known as guanylyl cyclase-A, is a transmembrane receptor guanylyl cyclase that is activated by the cardiac hormones atrial natriuretic peptide and B-type natriuretic peptide. Although ligand-dependent NPR-A degradation (also known as down-regulation) is widely acknowledged in human and animal models of volume overload, down-regulation in cultured cells is controversial. Here, we examined the effect of ANP exposure on cellular NPR-A levels as a function of time. Relative receptor concentrations were estimated using guanylyl cyclase and immunoblot assays in a wide variety of cell lines that endogenously or exogenously expressed low or high numbers of receptors. ANP exposures of 1 h markedly reduced hormone-dependent but not detergent-dependent guanylyl cyclase activities in membranes from exposed cells. However, 1-h ANP exposures did not significantly reduce NPR-A concentrations in any cell line. In contrast, exposures of greater than 1 h reduced receptor concentrations in a time-dependent manner. The time required for half of the receptors to be degraded (t1/2) in primary bovine aortic endothelial and immortalized HeLa cells was approximately 8 h. In contrast, a 24-h exposure of ANP to 293T cells stably overexpressing NPR-A caused less than half of the receptors to be degraded. To our knowledge, this is the first report to directly measure NPR-A down-regulation in endogenously expressing cells. We conclude that down-regulation is a universal property of NPR-A but is relatively slow and varies with receptor expression levels and cell type.

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