Homologous IRCM-Serine Protease 1 from pituitary, heart atrium and ventricle: A common pro-hormone maturation enzyme?

1986 ◽  
Vol 6 (9) ◽  
pp. 835-844 ◽  
Author(s):  
Nabil G. Seidah ◽  
James A. Cromlish ◽  
Josée Hamelin ◽  
Gaétan Thibault ◽  
Michel Chrétien
Keyword(s):  
Serine Protease ◽  
Rat Heart ◽  
Atrial Natriuretic Factor ◽  
Cleavage Sites ◽  
Heart Atrium ◽  
Natriuretic Factor ◽  
Heart Atria ◽  
Atrial Natriuretic

IRCM-Serine Protease 1 (IRCM-SP1) has recently been isolated and characterized from porcine pituitary anterior and neurointermediate lobes (Cromlish et al., 1986a, J. Biol. Chem.261:10850–10858; Cromlish et al., 1986b, J. Biol. Chem.261:10859–10870). This pituitary serine protease was shown to selectively cleave human proopiomelanocortin (POMC)-derived peptides at both pairs of basic residues and C-terminal to specific Arg residues, all known to be cleaved in vivo. Here, a similar enzyme was isolated from rat heart atria and ventricles. Rat IRCM-SP1 was shown to be highly specific for the same cleavage sites in POMC, as the porcine pituitary homologue. Furthermore, the rat and the porcine enzymes cleave rat pro-Atrial Natriuretic Factor (pro-ANF 1–126) to yield ANF 103–126, 102–126 and 99–126 in that order of preference. This suggests that in vitro the cleavage sites preferred in pro-ANF resemble those found in brain and hypothalamus. The enzyme is nine times more abundant in atria versus ventricles/mg protein. It is concluded that IRCM-SP1, could well represent a common pro-hormone maturation enzyme for POMC and Pro-ANF and possibly many other pro-hormones.

Inactivation of atrial natriuretic factor in blood

1985 ◽  
Vol 63 (12) ◽  
pp. 1615-1617 ◽  
Author(s):  
Anthony T. Veress ◽  
Chee K. Chong ◽  
Harald Sonnenberg
Keyword(s):  
Rat Heart ◽  
Atrial Natriuretic Factor ◽  
Physiological Role ◽  
White Cell ◽  
Tissue Extracts ◽  
Natriuretic Factor ◽  
Blood Elements ◽  
Heart Atria ◽  
Atrial Natriuretic

Tissue extracts of rat heart atria contain a family of peptides with natriuretic and vasorelaxant properties. It has been shown by others that inactivation of this atrial natriuretic factor may involve endogenous peptidases. The present experiments demonstrate that incubation in blood in vitro reduces the natriuretic activity of the factor. Specifically, inactivation was associated with a white cell/platelet fraction, indicating that these blood elements may play a physiological role in the metabolism of this new putative hormone.

Atrial natriuretic factor binding sites in the jejunum

1989 ◽  
Vol 256 (2) ◽  
pp. G436-G441 ◽  
Author(s):  
C. Bianchi ◽  
G. Thibault ◽  
A. De Lean ◽  
J. Genest ◽  
M. Cantin
Keyword(s):  
Binding Sites ◽  
Atrial Natriuretic Factor ◽  
Specific Binding ◽  
Rat Tissues ◽  
Rat Jejunum ◽  
Specific Binding Sites ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

We have studied the localization and the characterization of atrial natriuretic factor (ANF) binding sites by radioautographic techniques. Quantitative in vitro radioautography with a computerized microdensitometer demonstrated the presence of high-affinity, low-capacity 125I-ANF-(99-126) binding sites (Kd, 48 pM; Bmax, 63 fmol/mg protein) mainly in the villi of 20-microns slide-mounted transverse sections of the rat jejunum. Competition curves showed 50% inhibitory concentrations of 55 and 1,560 pM for ANF-(99-126) and ANF-(103-123), respectively. In vivo electron microscope radioautography showed that 80% of the silver grains were localized on the lamina propria fibroblast-like cells, 18% on mature enterocytes, and 2% on capillaries. Bradykinin and adrenocorticotropin did not compete with ANF binding. These results demonstrate that ANF binding sites in the rat jejunum possess the pharmacological characteristics of functional ANF receptors encountered in other rat tissues, and ultrastructural radioautographs show their cellular distribution. Taken together, these results demonstrate the presence and the localization of specific binding sites for ANF in the jejunal villi of the rat small intestine.

In vitro secretion of atrial natriuretic factor: receptor-mediated release of prohormone

1988 ◽  
Vol 254 (5) ◽  
pp. R809-R814 ◽  
Author(s):  
A. T. Veress ◽  
S. Milojevic ◽  
C. Yip ◽  
T. G. Flynn ◽  
H. Sonnenberg
Keyword(s):  
Atrial Natriuretic Factor ◽  
Active Form ◽  
High Concentration ◽  
Natriuretic Factor ◽  
Rat Hearts ◽  
Agonist Concentration ◽  
Atrial Natriuretic Factor Receptor ◽  
Atrial Natriuretic

Secretion of atrial natriuretic factor (ANF) in vivo is thought to be mediated by atrial distension. We have shown previously that nonstretched atria can release natriuretic activity in vitro when stimulated by certain agonists. In the present study atrial appendages from freshly excised rat hearts were incubated at 37 degrees C for up to 1 h in the presence of either vasopressin (5 X 10(-9) mol/l) or angiotensin II (2.5 X 10(-7) mol/l). Aliquots of postincubation media were injected intravenously into anesthetized bioassay rats to determine natriuretic activity. Control media, in which atria had been incubated without agonist, did not cause natriuresis. Significant increases in sodium excretion were seen after injection of media in which atria had been incubated in the presence of either agonist. Injection of medium with the same agonist concentration did not result in comparable natriuresis. Radioimmunoassay (RIA) indicated a high concentration of immunoactive ANF in the natriuretic media. However, radioreceptor assay (RRA) of the same media gave apparent ANF concentrations that were lower by about three orders of magnitude. Because the antibody used in the RIA cross reacts with ANF prohormone, whereas the RRA is sensitive only to the active form, we concluded that agonist-induced, stretch-independent release of ANF is in the form of prohormone, which can be converted to the active hormone in the circulation of the bioassay animal. The conclusion of prohormone release was confirmed by liquid chromatography. The data thus suggest that receptor-mediated as well as stretch-induced ANF secretion may be important in regulating the activity of the ANF system.

scholarly journals Degradation of atrial natriuretic factor in the rat

1986 ◽  
Vol 240 (2) ◽  
pp. 461-469 ◽  
Author(s):  
K K Murthy ◽  
G Thibault ◽  
R Garcia ◽  
J Gutkowska ◽  
J Genest ◽  
...  
Keyword(s):  
Whole Blood ◽  
Atrial Natriuretic Factor ◽  
Mesenteric Artery ◽  
Biologically Active ◽  
Prolonged Incubation ◽  
Amino Acid Peptide ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

The biologically active circulating form of atrial natriuretic factor (ANF) in the rat is the 28-amino-acid peptide ANF-(Ser-99-Tyr-126). Degradation of this peptide in vivo as well as in vitro, in whole blood, in plasma and by the isolated mesenteric artery was investigated. Studies in vivo in the rat demonstrated that the elimination and degradation of ANF was extremely fast: within 3 min more than 95% of the injected immunoreactive material was eliminated from circulation. The production of a short C-terminal peptide was detected on injection of 125I-ANF-(Ser-99-Tyr-126) into the rat. This peptide increased proportionately with incubation time. Experiments in vitro in the presence of whole blood or plasma did not cause any major destruction of ANF even after incubation for 60 min. After this prolonged incubation in plasma, ANF-(Ser-99-Tyr-126) was partially converted into ANF-(Ser-103-Tyr-126), a less potent peptide. Isolated mesenteric-artery preparation appeared to degrade ANF in a manner very similar to the system in vivo. These results suggest that degradation of ANF may occur either after internalization in the vascular cells or by a membrane-bound enzyme in the vasculature.

Human heart LIM protein activates atrial-natriuretic-factor gene expression by interacting with the cardiac-restricted transcription factor Nkx2.5

2008 ◽  
Vol 409 (3) ◽  
pp. 683-690 ◽  
Author(s):  
Bin Zheng ◽  
Mei Han ◽  
Jin-kun Wen ◽  
Rui Zhang
Keyword(s):  
Transcription Factor ◽  
Atrial Natriuretic Factor ◽  
Human Heart ◽  
Specific Expression ◽  
Human Embryonic Kidney Cells ◽  
Factor Gene ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

hhLIM [human heart LIM (Lin-11/IsI-1/Mec-3) protein] is a muscle-specific LIM-only protein that consists of two LIM motifs. hhLIM functions as a positive regulator for cardiac hypertrophy. Here we report that hhLIM serves as a cofactor regulating the expression of the ANF (atrial natriuretic factor) gene in H9c2 rat cardiomyoblast cells. We found that hhLIM promoted the expression of the ANF gene in H9c2 cells, but not in A293 human embryonic kidney cells. Furthermore, we showed that hhLIM interacted with Nkx2.5 (a cardiac-restricted transcription factor) in vivo and in vitro using its N-terminal LIM domain and enhanced the binding ability of Nkx2.5 to the NKE (Nkx2.5-binding element) boxes in the ANF promoter. These results suggest that hhLIM promotes the specific expression of the ANF gene by co-operating with Nkx2.5.

Inhibition of Neutral Endopeptidase (EC 3.4.24.11) Leads to An Atrial Natriuretic Factor-Mediated Natriuretic, Diuretic and Antihypertensive Response in Rodents

1991 ◽  
Vol 80 (3) ◽  
pp. 265-269 ◽  
Author(s):  
N. B. Shepperson ◽  
P. L. Barclay ◽  
J. A. Bennett ◽  
G. M. R. Samuels
Keyword(s):  
Atrial Natriuretic Factor ◽  
Neutral Endopeptidase ◽  
Volume Loading ◽  
Natriuretic Factor ◽  
Anaesthetized Rats ◽  
Diuretic Response ◽  
Antihypertensive Response ◽  
Atrial Natriuretic

1. Atrial natriuretic factor is metabolized by neutral endopeptidase (atriopeptidase; EC 3.4.24.11) in vitro. Inhibitors of this enzyme have been reported to prolong the half-life of atrial natriuretic factor in vivo and to potentiate the renal and haemodynamic effects of exogenous atrial natriuretic factor. 2. (±)-Candoxatrilat, a selective neutral endopeptidase inhibitor, potentiated the natriuretic and diuretic response to volume loading in anaesthetized rats. Part of the response to volume loading and the potentiation by (±)-candoxatrilat was prevented by a polyclonal atrial natriuretic factor antiserum. The diuretic and natriuretic responses evoked by hydrochlorothiazide were not altered by the antiserum. 3. (±)-Candoxatrilat reduced systolic blood pressure of one-kidney deoxycorticosterone acetate-salt hypertensive rats for over 5 h. This response was abolished by pretreatment with atrial natriuretic factor antiserum. 4. These data demonstrate that the neutral endopeptidase inhibitor (±)-candoxatrilat has natriuretic/diuretic and antihypertensive effects in rodents, and that these effects are mediated via endogenous atrial natriuretic factor.

Platelet-activating factor stimulates the release of atrial natriuretic factor from the rat heart

1991 ◽  
Vol 130 (2) ◽  
pp. 281-288 ◽  
Author(s):  
T. E. Rayner ◽  
M. F. Menadue ◽  
J. R. Oliver
Keyword(s):  
Rat Heart ◽  
Atrial Natriuretic Factor ◽  
Isolated Heart ◽  
Platelet Activating Factor ◽  
Natriuretic Factor ◽  
Paf Receptor ◽  
Factor Α ◽  
Paf Receptor Antagonist ◽  
Atrial Natriuretic

ABSTRACT Atrial natriuretic factor (α-ANF(99–126); ANF) is released from atrial cells following atrial distension, myocardial infarction and periods of ischaemic or tachyarrhythmias. In this report we demonstrate that platelet-activating factor (PAF) stimulates ANF release from the isolated perfused rat heart and following i.v. injection to conscious unrestrained rats. ANF release peaked at 145% above baseline following injection of 2·5 nmol PAF into the isolated heart while administration of 2 nmol in vivo produced a 135% increase in plasma ANF levels. The PAF receptor antagonist BN52021 (10 μmol/l) attenuated this stimulated release, with the results suggesting a role for PAF in ANF secretion following release from damaged myocardium or as a humoral factor originating from the kidney. Journal of Endocrinology (1991) 130, 281–288

scholarly journals Endothelin in a model of acute ischemic renal dysfunction: modulating action of atrial natriuretic factor.

1992 ◽  
Vol 3 (2) ◽  
pp. 196-202 ◽  
Author(s):  
E K Sandok ◽  
A Lerman ◽  
A J Stingo ◽  
M A Perrella ◽  
P Gloviczki ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Renal Dysfunction ◽  
Atrial Natriuretic Factor ◽  
Renal Vasoconstriction ◽  
Natriuretic Factor ◽  
Group I ◽  
Change In Mean ◽  
Atrial Natriuretic

This study was undertaken to investigate circulating endothelin (ET) and associated renal hemodynamics in the acute ischemic renal dysfunction associated with suprarenal aortic cross-clamping (ACC) in the presence and absence of prostaglandin inhibition in the anesthetized dog. Second, the modulating action of exogenous atrial natriuretic factor (ANF) was also investigated. In Group I (ACC; N = 6), ACC was performed in the absence of prostaglandin inhibition. No change in mean arterial pressure, GFR, RBF, renal vascular resistance, or ET was noted 2 h after reperfusion when compared with baseline values. In the presence of prostaglandin inhibition with indomethacin (10 mg/kg iv) (Group II, ACC + INDO; N = 10), an increase in plasma ET was first noted to be elevated above baseline ET in Group I as well as during and 2 h after ACC in association with a reduction in GFR, marked renal vasoconstriction, and a sustained increase in arterial pressure. To evaluate the role of the kidney in this increase in ET, another group (Group III, ACC + INDO + NEPH; N = 6) was investigated in the presence of prostaglandin inhibition, and bilateral renal artery clamping was performed 30 min before ACC and maintained throughout the protocol to simulate nephrectomy. In this group, plasma ET concentrations did not increase during ACC. Because ANF may antagonize the renal actions of ET in vivo and may suppress ET release in vitro, the action of ANF upon GFR and plasma ET was evaluated in Group IV (ACC + INDO + ANF; N = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

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