Natriuretic peptides inhibit rat astroglial proliferation: mediation by C receptor

1991 ◽  
Vol 261 (2) ◽  
pp. R453-R457 ◽  
Author(s):  
E. R. Levin ◽  
H. J. Frank
Keyword(s):  
Growth Factor ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Thymidine Incorporation ◽  
Primary Cultures ◽  
Physiological Role ◽  
Brain Cell ◽  
Bovine Brain ◽  
High Affinity ◽  
Capillary Endothelial Cells

The processing and secretion of atrial natriuretic peptide (ANP) from neurons and the expression of high-affinity receptors on astroglia from primary cultures of fetal rat diencephalon have recently been demonstrated. Thus natriuretic peptides may play a role in neuronal-glial signaling, but a physiological role has not been characterized. In these studies, we show that ANP and brain natriuretic peptide significantly (P less than 0.05) decrease the incorporation of [3H]thymidine into astroglia in the presence of fetal bovine serum and inhibit the proliferation of these cells in the presence or absence of serum. These effects were evident at concentrations of natriuretic peptides (10(-10) M) characteristic of the receptor Kd and were not seen in cultured bovine brain capillary endothelial cells, another brain cell expressing high-affinity receptors for the natriuretic peptides. The antiproliferative effects were potently produced by ANP-(4-23), a ring-deleted analogue of ANP-(1-28), which at the concentrations used in this study binds only to the C or low-molecular-weight natriuretic peptide receptor. Thymidine incorporation was not affected by adenosine 3',5'-cyclic monophosphate (cAMP), the inhibition of which has been proposed to mediate postbinding signaling of the C receptor. Epidermal growth factor (10(-9) M) produced an 87% increase in thymidine incorporation, which was not significantly inhibited by either form of ANP. Thus natriuretic peptides in the brain may serve as antigrowth factors for glia through binding to a receptor previously felt to function solely in peptide clearance. The inhibitory effects are not the result of inhibiting the proliferative effects of an endogenous growth factor and are cAMP independent.

scholarly journals Physiology and clinical importance of the natriuretic peptide system

2011 ◽  
Vol 152 (26) ◽  
pp. 1025-1034
Author(s):  
Gábor Szabó ◽  
János Rigó jr. ◽  
Bálint Nagy
Keyword(s):  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Physiological Role ◽  
Clinical Importance ◽  
The Body ◽  
Diagnosis And Prognosis ◽  
Peptide Family ◽  
Peptide System ◽  
Pressure Changes

In the last three decades many members of the natriuretic peptide family was isolated. The function and physiological role of these peptides are pleiotropic. All natriuretic peptides are synthesized from polypeptide precursors. Together with the sympathetic nervous system and other hormones they play key roles, like an endogenous system in the regulation of the body fluid homeostasis and blood pressure. Changes in this balance lead to dysfunction in the endothel and left ventricle, which can cause severe complications. In many cardiovascular diseases natriuretic peptides serve not only as marker for diagnosis and prognosis but they have therapeutic importance. In the last years the potential use of the elevated BNP levels for diagnosis of pre-eclampsia was examined. In our review we discuss the current understanding of molecular biology, biochemistry and clinical relevance of natriuretic peptides. Orv. Hetil., 2011, 152, 1025–1034.

scholarly journals Identification and characterization of receptors specific for human pancreatic secretory trypsin inhibitor.

1990 ◽  
Vol 172 (4) ◽  
pp. 1133-1142 ◽  
Author(s):  
T Niinobu ◽  
M Ogawa ◽  
A Murata ◽  
J Nishijima ◽  
T Mori
Keyword(s):  
Growth Factor ◽  
Trypsin Inhibitor ◽  
Thymidine Incorporation ◽  
Specific Binding ◽  
Membrane Receptors ◽  
Scatchard Analysis ◽  
Dependent Manner ◽  
Pancreatic Secretory Trypsin Inhibitor ◽  
High Affinity ◽  
Dose Dependent

Specific binding sites for human pancreatic secretory trypsin inhibitor (PSTI) on 3T3 Swiss albino cells were studied using radioiodinated recombinant PSTI. Some ion species, pH, and temperature significantly influenced the binding of 125I-PSTI. Kinetic studies showed that the binding of 125I-PSTI to 3T3 Swiss albino cells reached the maximum level within 120 min at 4 degrees C, with a slow dissociation rate. The half-maximal inhibition (ID50) of 125I-PSTI binding by unlabeled PSTI occurred at 1.0 x 10(-10) M. On Scatchard analysis of the competitive binding data, linear plots indicated a single class of receptors with high affinity (Kd = 5.3 x 10(-10) M) on 3T3 Swiss albino cells, the number of receptors being 5,400 per cell. Treatment of surface-bound radiolabeled PSTI with a chemical crosslinker (disuccinimidyl suberate) led to the identification of a membrane polypeptide of Mr 140,000 to which PSTI was crosslinked. The formation was inhibited by an excess amount of unlabeled PSTI in a dose-dependent manner. The binding of 125I-PSTI to 3T3 Swiss albino cells was competitively inhibited by unlabeled PSTI but not by other peptide hormones, such as epidermal growth factor (EGF), bovine fibroblast growth factor, insulin-like growth factor, transforming growth factor alpha, platelet-derived growth factor, and tumor necrosis factor, indicating the presence of receptors specific for PSTI. Various protease inhibitors had no or only a little effect, and mercaptoethanol and dithiothreitol strongly decreased the binding of 125I-PSTI. Incubation at 37 degrees C resulted in rapid internalization of cell-bound 125I-PSTI, followed by the appearance of trichloroacetic acid-soluble 125I-radioactivity in the culture medium, due to degradation of internalized PSTI. In addition, PSTI stimulated [3H]thymidine incorporation into DNA on 3T3 Swiss albino cells in a dose-dependent manner. The combined addition of PSTI and EGF stimulated [3H]thymidine incorporation to an extent greater than that seen with either agent alone. These results indicated that the biological effect of PSTI was mediated by high affinity plasma membrane receptors, which were not a cell-surface proteinase(s). Specific binding of 125I-PSTI was noted with the following cells: WI-38, 3T3 Swiss albino, HUVE, BDC-1, and H4-II-E-C3.

scholarly journals Total NT-proBNP, a novel biomarker related to recurrent atrial fibrillation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lidia Staszewsky ◽  
Jennifer M. T. A. Meessen ◽  
Deborah Novelli ◽  
Ursula-Henrike Wienhues-Thelen ◽  
Marcello Disertori ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Regression Analysis ◽  
Growth Factor ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Binding Protein ◽  
Circulating Biomarkers ◽  
Total N ◽  
Fatty Acid Binding ◽  
Recurrent Atrial Fibrillation

Abstract Background Novel circulating biomarkers may help in understanding the underlying mechanisms of atrial fibrillation (AF), a challenge for AF management and prevention of cardiovascular (CV) events. Whether glycosylation affects the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in AF is still unknown. Objectives To test how deglycosylated total NT-proBNP, NT-proBNP and a panel of biomarkers are associated with: (1) recurrent AF, (2) first hospitalization for CV reasons. Methods A total of 382 patients of the GISSI-AF trial in sinus rhythm with a history of AF, echocardiographic variables, total NT-proBNP, NT-proBNP and nine additional biomarkers [Total N-terminal pro-B type natriuretic peptide (Total NT proBNP), N-terminal pro-B type natriuretic peptide (NTproBNP), Angiopoietin 2 (Ang2), Bone morphogenic protein-10 (BMP10), Dickkopf-related protein-3 (DKK3), Endothelial cell specific molecule-1 (ESM1), Fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor-15 (GDF15), Insulin-like growth factor-binding protein-7 (IGFBP7) and Myosin binding protein C3 (MYPBC3)]. were assayed at baseline, 6 and 12 months under blind conditions in a laboratory at Roche Diagnostics, Penzberg, Germany. The associations between circulating biomarkers and AF at the 6- and 12-month visits, and their predictive value, were assessed in multivariable models with logistic regression analysis and Cox proportional hazards regression analysis. Biomarkers associations were modelled for 1SD increase in their level. Results Over a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for CV reasons. Total NT-proBNP, NT-proBNP, Ang2 and BMP10 showed the strongest associations with ongoing AF. Natriuretic peptides also predicted recurrent AF (total NT-proBNP: HR:1.19[1.04–1.36], p = 0.026; NT-proBNP: HR:1.19[1.06–1.35], p = 0.016; Ang2: HR:1.07[0.95–1.20], p = 0.283; BMP10: HR:1.09[0.96–1.25], p = 0.249) and CV hospitalization (total NT-proBNP: HR:1.57[1.29–1.90], p < 0.001 1.63], p = 0.097). Conclusions The association of total NT-proBNP with the risk of AF first recurrence was similar to that of NT-proBNP, suggesting no influence of glycosylation. Analogous results were obtained for the risk of first hospitalization for CV reasons. Natriuretic peptides, Ang2 and BMP10 were associated with ongoing AF. Findings from the last two biomarkers point to a pathogenic role of cardiac extracellular matrix and cardiomyocyte growth in the myocardium of the right atrium and ventricle.

scholarly journals Natriuretic peptides are neuroprotective on in vitro models of PD and promote dopaminergic differentiation of hiPSCs-derived neurons via the Wnt/β-catenin signaling

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Daniela Giovannini ◽  
Federica Andreola ◽  
Paola Spitalieri ◽  
Ewa Krystyna Krasnowska ◽  
Arianna Colini Baldeschi ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Primary Cultures ◽  
In Vitro Models ◽  
Neural Population ◽  
Symptomatic Therapy ◽  
Brain Functions ◽  
Dopaminergic Differentiation

AbstractOver the last 20 years, the efforts to develop new therapies for Parkinson’s disease (PD) have focused not only on the improvement of symptomatic therapy for motor and non-motor symptoms but also on the discovering of the potential causes of PD, in order to develop disease-modifying treatments. The emerging role of dysregulation of the Wnt/β-catenin signaling in the onset and progression of PD, as well as of other neurodegenerative diseases (NDs), renders the targeting of this signaling an attractive therapeutic opportunity for curing this brain disorder. The natriuretic peptides (NPs) atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), are cardiac and vascular-derived hormones also widely expressed in mammalian CNS, where they seem to participate in numerous brain functions including neural development/differentiation and neuroprotection. We recently demonstrated that ANP affects the Wnt/β-catenin pathway possibly through a Frizzled receptor-mediated mechanism and that it acts as a neuroprotective agent in in vitro models of PD by upregulating this signaling. Here we provide further evidence supporting the therapeutic potential of this class of natriuretic hormones. Specifically, we demonstrate that all the three natriuretic peptides are neuroprotective for SHSY5Y cells and primary cultures of DA neurons from mouse brain, subjected to neurotoxin insult with 6-hydroxydopamine (6-OHDA) for mimicking the neurodegeneration of PD, and these effects are associated with the activation of the Wnt/β-catenin pathway. Moreover, ANP, BNP, CNP are able to improve and accelerate the dopaminergic differentiation and maturation of hiPSCs-derived neural population obtained from two differed healthy donors, concomitantly affecting the canonical Wnt signaling. Our results support the relevance of exogenous ANP, BNP, and CNP as attractive molecules for both neuroprotection and neurorepair in PD, and more in general, in NDs for which aberrant Wnt signaling seems to be the leading pathogenetic mechanism.

Distinct receptors for epidermal growth factor-urogastrone in cultured gastric smooth muscle cells

1991 ◽  
Vol 260 (6) ◽  
pp. G827-G834
Author(s):  
S. G. Yang ◽  
M. D. Hollenberg
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Guinea Pig ◽  
Thymidine Incorporation ◽  
Circular Muscle ◽  
Relative Order ◽  
Binding Affinities ◽  
High Affinity ◽  
Epidermal Growth

We describe a propagable cell strain from guinea pig gastric circular muscle (GCM), which we have characterized in terms of its smooth muscle phenotype and its binding and biological response (thymidine incorporation) to epidermal growth factor-urogastrone (EGF-URO) and transforming growth factor-alpha (TGF-alpha). The binding of 125I-labeled EGF-URO to the GCM cells exhibited high affinity and an appropriate peptide specificity. A curvilinear Scatchard plot of the binding data indicated two classes of high-affinity binding sites (dissociation constants of 0.69 and 4.3 nM) and a maximal binding capacity of 24,000 sites/cell. Binding competition data demonstrated that the binding affinity of TGF-alpha was greater than that of EGF-URO by a factor of 2. These relative binding affinities agreed with the two- to threefold greater potency of TGF-alpha, compared with EGF-URO, for the stimulation of GCM thymidine incorporation. The relative order of binding affinity and biological potency (TGF-alpha greater than EGF-URO) was distinct from the relative order of binding affinities (EGF-URO greater than TGF-alpha) observed using guinea pig liver and human placental membrane preparations. We conclude that the cultured smooth muscle-derived GCM cells possess a receptor subtype that is in accord with contractile bioassay data obtained previously with intact gastric circular muscle strips. This receptor (TGF-alpha greater than EGF-URO) appears distinct from the one previously characterized in nonmuscle tissues.

Identification of an EGF/TGF-alpha receptor in primary cultures of guinea pig gastric mucous epithelial cells

1996 ◽  
Vol 270 (4) ◽  
pp. G604-G612 ◽  
Author(s):  
M. J. Rutten ◽  
P. J. Dempsey ◽  
C. A. Luttropp ◽  
M. A. Hawkey ◽  
B. C. Sheppard ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Guinea Pig ◽  
Transforming Growth Factor ◽  
Primary Cultures ◽  
Physiological Role ◽  
Scatchard Analysis ◽  
Binding Studies ◽  
Significant Difference ◽  
Gastric Mucous

Binding and localization of transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) were assessed using in vitro primary cultures of guinea pig gastric mucous epithelial cells (GMEC). GMEC were isolated and cultured in six-well plates with Dulbecco's modified Eagle's medium + 10% serum and then changed to serum-free medium for 24 h for binding studies. The binding time course of 125I-labeled EGF and 125I-TGF-alpha in GMEC cultures at 4 degrees C was saturable, reaching a plateau within 4-6 h. Competition-binding curves revealed that the amount of unlabeled EGF and TGF-alpha to reduce 125I-EGF binding by 50% was 0.35 and 0.23 nM, respectively. The amount of unlabeled EGF and TGF-alpha to decrease 125I-TGF-alpha binding by 50% was 0.30 and 0.21 nM, respectively. A Scatchard analysis of the data disclosed that a single class of high-affinity binding sites (dissociation constant = 0.24 nM) was present. The maximal binding capacity was approximately 20 fmol/10(6) cells or approximately 12,000 receptors per cell. The binding of 125I-EGF and 125I-TFG-alpha to GMEC cultures was maximal between pH 7.0 and 8.5. No specific binding of EGF or TGF-alpha could be detected below pH 5.0. The half-maximal pH dissociation value for EGF and TGF-alpha was pH 5.89 and pH 6.83, respectively. We found no difference in the final amounts of membrane-bound or internalized 125I-EGF and 125I-TGF-alpha. However, there was a significant difference (P < 0.05) at 5-30 min in the rate of dissociated and internalized 125I-EGF- and 125I-TGF-alpha. Immunofluorescence microscopy of GMEC cultures for EGF/TGF-alpha receptors showed increased fluorescence at the leading edges and around the perimeter of cells. Detection of an EGF/TGF-alpha receptor was also confirmed by Western blotting. Our findings demonstrate that guinea pig GMEC possess a specific EGF/TGF-alpha receptor, which further supports a physiological role for EFG and TFG-alpha as mitogens in these cells.

A C TYPE NATRIURETIC PEPTIDE IS A VASODILATOR IN VIVO AND IN VITRO IN THE COMMON DOGFISH

1992 ◽  
Vol 133 (2) ◽  
pp. R1-R4 ◽  
Author(s):  
C. Bjenning ◽  
Y. Takei ◽  
T.X. Watanabe ◽  
K. Nakajima ◽  
S. Sakakibara ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Physiological Role ◽  
Arterial Blood ◽  
Brain Natriuretic Peptides ◽  
Dose Dependent

ABSTRACT The effects of an elasmbranch cardiac C-type natriuretic peptide (dogfish CNP-22) on arterial blood pressure were investigated in vivo in chronically cannulated dogfish Scyliorhinus canicula and in vitro by a myographic technique using the distal part of the first branchial artery. In-vivo dogfish CNP-22 caused a dose-dependent reduction in mean arterial blood pressure which was much more potent than that of α-human ANP. In-vitro dogfish CNP-22 also caused a dose-dependent relaxation which was independent of the endothelium. These results are in marked contrast to those obtained in similar studies on other vertebrate species in which CNP exhibited only mild hypotensive effects compared to both atrial and brain natriuretic peptides. This study indicates the importance of using homologous peptides in determing the physiological role of natriuretic peptides in non-mammalian vertebrates.

Natriuretic peptide receptors in the fetal rat

1995 ◽  
Vol 269 (2) ◽  
pp. E253-E268 ◽  
Author(s):  
J. Brown ◽  
Z. Zuo
Keyword(s):  
Sodium Dodecyl Sulfate ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Binding Sites ◽  
Gel Electrophoresis ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Cyclic Monophosphate ◽  
High Affinity

In vitro autoradiography of rat fetuses from embryonic days 12-19 (E12-E19) showed widespread high-affinity specific binding sites for natriuretic peptides. The sites on E16 somites avidly bound C-type natriuretic peptide [CNP-(1-22)] as well as C-ANP, a synthetic ligand that selects the C-type natriuretic peptide receptor (NPR-C). Most somitic binding sites had high affinity for atrial natriuretic peptide [ANP-(1-28)], confirming their resemblance to NPR-C. A few had a lower apparent affinity for ANP-(1-28), suggesting that they might be NPR-B. CNP-(1-22) was more powerful than ANP-(1-28) as an agonist of guanosine 3',5'-cyclic monophosphate production in somites, and ATP augmented the action of CNP-(1-22). These observations further suggest the presence of NPR-B. However, with cross-linking of 3-[125I]iodo-0-tyrosyl rat CNP-(1-22) to somitic membranes followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, only a single 64-kDa binding protein was detected under reducing conditions. This is not consistent with intact approximately 120-kDa NPR-B. In vitro autoradiography of the binding of natriuretic peptides to E16 liver implied the presence of NPR-A and NPR-C-like receptors. Hepatic guanosine 3',5'-cyclic monophosphate production was most powerfully stimulated by ANP-(1-28), as expected for NPR-A. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis also identified NPR-A and NPR-C-like proteins in E16 hepatic membranes. Thus different NPRs are expressed by specific fetal tissues. This may be developmentally significant.

Paracrine control of gastric epithelial cell growth in culture by transforming growth factor-alpha

1993 ◽  
Vol 264 (2) ◽  
pp. G390-G396 ◽  
Author(s):  
M. C. Chen ◽  
A. T. Lee ◽  
W. E. Karnes ◽  
D. Avedian ◽  
M. Martin ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cell Growth ◽  
Transforming Growth Factor ◽  
Cultured Cells ◽  
Thymidine Incorporation ◽  
Primary Cultures ◽  
Transforming Growth Factor Alpha ◽  
Mucosal Cell ◽  
Factor Alpha

Studying primary cultures of replicating canine oxyntic mucosal cells, we found evidence for modulation of cell growth by endogenous factors. [3H]thymidine incorporation into DNA was rapid with cells cultured in medium free of serum or added growth factors, and growth rates of these cultures were markedly dependent on plating density, indicating mitogenic control by soluble endogenous growth factors. Data indicated that endogenous transforming growth factor-alpha (TGF-alpha) exerted mitogenic control under the following conditions. 1) TGF-alpha was detected in the cultured cells by radioimmunoassay and immunohistochemistry. 2) TGF-alpha-like immunoreactivity and receptor reactivity were present in the medium in concentrations sufficient to exert mitogenic control. 3) Receptors for TGF-alpha and epidermal growth factor (EGF) were present in the cultures. 4) Immunoabsorption by a TGF-alpha-specific antisera reduced [3H]thymidine incorporation. TGF-alpha was localized to parietal cells by immunohistochemistry and cell separation. In contrast, combined [3H]thymidine autoradiography and immunohistochemistry with anti-TGF-alpha did not detect TGF-alpha in dividing cells. We conclude that parietal cell TGF-alpha exerts paracrine control of mucosal cell growth in vitro, and we speculate that this is an important paracrine mechanism in vivo.

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