Atrial natriuretic factor stimulates exocrine pancreatic secretion in the rat through NPR-C receptors

2003 ◽  
Vol 285 (5) ◽  
pp. G929-G937 ◽  
Author(s):  
María E. Sabbatini ◽  
Alberto Villagra ◽  
Carlos A. Davio ◽  
Marcelo S. Vatta ◽  
Belisario E. Fernández ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pancreatic Secretion ◽  
Intracellular Signaling ◽  
Atrial Natriuretic Factor ◽  
Adrenergic Blockade ◽  
Exocrine Pancreatic Secretion ◽  
Pancreatic Acini ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

Increasing evidence supports the role of atrial natriuretic factor (ANF) in the modulation of gastrointestinal physiology. The effect of ANF on exocrine pancreatic secretion and the possible receptors and pathways involved were studied in vivo. Anesthetized rats were prepared with pancreatic duct cannulation, pyloric ligation, and bile diversion into the duodenum. ANF dose-dependently increased pancreatic secretion of fluid and proteins and enhanced secretin and CCK-evoked response. ANF decreased chloride secretion and increased the pH of the pancreatic juice. Neither cholinergic nor adrenergic blockade affected ANF-stimulated pancreatic secretion. Furthermore, ANF response was not mediated by the release of nitric oxide. ANF-evoked protein secretion was not inhibited by truncal vagotomy, atropine, or Nω-nitro-l-arginine methyl ester administration. The selective natriuretic peptide receptor-C (NPR-C) receptor agonist cANP-(4–23) mimicked ANF response in a dose-dependent fashion. When the intracellular signaling coupled to NPR-C receptors was investigated in isolated pancreatic acini, results showed that ANF did not modify basal or forskolin-evoked cAMP formation, but it dose-dependently enhanced phosphoinositide hydrolysis, which was blocked by the selective PLC inhibitor U-73122. ANF stimulated exocrine pancreatic secretion in the rat, and its effect was not mediated by nitric oxide or parasympathetic or sympathetic activity. Furthermore, CCK and secretin appear not to be involved in ANF response. Present findings support that ANF exerts a stimulatory effect on pancreatic exocrine secretion mediated by NPR-C receptors coupled to the phosphoinositide pathway.

Atrial natriuretic factor negatively modulates secretin intracellular signaling in the exocrine pancreas

2007 ◽  
Vol 292 (1) ◽  
pp. G349-G357 ◽  
Author(s):  
María E. Sabbatini ◽  
Marcelo S. Vatta ◽  
Carlos A. Davio ◽  
Liliana G. Bianciotti
Keyword(s):  
Intracellular Signaling ◽  
Atrial Natriuretic Factor ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Signaling Mechanism ◽  
Pancreatic Acini ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

We previously reported that atrial natriuretic factor (ANF) stimulates pancreatic secretion through NPR-C receptors coupled to PLC and potentiates secretin response without affecting cAMP levels. In the present study we sought to establish the intracellular signaling mechanism underlying the interaction between both peptides. In isolated pancreatic acini 100 nM ANF abolished cAMP accumulation evoked by any dose of secretin. Lower doses of ANF (1 fM, 1 pM, 1 and 10 nM) dose dependently reduced EC50 secretin-evoked cAMP. Although ANF failed to affect cAMP stimulated by amthamine (selective H2 agonist) or isoproterenol (β-adrenergic agonist), it abolished VIP-induced cAMP formation. ANF inhibitory effect was prevented by U-73122 (PLC inhibitor) and GF-109203X (PKC inhibitor) but unaltered by PKG and nitric oxide synthase inhibition, supporting that the PLC/PKC pathway mediated the effect. ANF response was mimicked by cANP (4–23 amide) and abolished by pertussis toxin, strongly supporting NPR-C receptor activation. In vivo studies showed that ANF at 0.5 μg·kg−1·h−1 enhanced secretion stimulated by 1 U·kg−1·h−1 secretin but at 1 and 2 μg·kg−1·h−1 it abolished secretin response. However, ANF at such doses failed to modify the secretion evoked by carbachol or CCK. Present results show that ANF negatively modulated secretin secretory response and intracellular signaling through the activation of NPR-C receptors coupled to the PLC/PKC pathway. Furthermore, the finding that ANF also inhibited VIP-evoked cAMP supports a selective modulation of class II G-protein coupled receptors by ANF. Present findings suggest that ANF may play a protective role by reducing secretin response to avoid overstimulation.

Atrial Natriuretic Factor and Angiotensin Ii Stimulate Nitric Oxide Release from Human Proximal Tubular Cells

1995 ◽  
Vol 89 (5) ◽  
pp. 527-531 ◽  
Author(s):  
J. S. McLay ◽  
P. K. Chatterjee ◽  
S. K. Mistry ◽  
R. P. Weerakody ◽  
A. G. Jardine ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Atrial Natriuretic Factor ◽  
Nitric Oxide Production ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Oxide Production ◽  
Natriuretic Factor ◽  
Proximal Tubular ◽  
Atrial Natriuretic

1. It has been recently reported that angiotensin II can enhance atrial natriuretic factor-stimulated cyclic GMP release from brain capillary endothelial cells and stimulate directly the release of cyclic GMP by Neuro 2a cells. A possible mechanism mediating such cyclic GMP release could be via the production of nitric oxide and the resultant stimulation of soluble guanylate cyclase. 2. The ability of angiotensin II, atrial natriuretic factor and c(4–23) atrial natriuretic factor to stimulate nitric oxide production was investigated in primary cultures of human proximal tubular cells. 3. Freshly prepared human proximal tubular cells were seeded onto 6-well plates and allowed to reach confluence. Cells were then incubated with incremental concentrations of either angiotensin II, atrial natriuretic factor or c(4–23) atrial natriuretic factor alone for 1, 4, 12 or 24 h or in the presence of the nitric oxide synthase inhibitor NG-monomethyl-l-arginine. Angiotensin II was also incubated with human proximal tubular cells in the presence of the AT, and AT2 receptor antagonists DuP 753 and PD 123319. 4. Incubation of human proximal tubular cells with angiotensin II, atrial natriuretic factor or c(4–23) atrial natriuretic factor produced a dose- and time-dependent increase in nitric oxide production, which was inhibited in the presence of NG-monomethyl-l-arginine. A similar increase in nitric oxide production was observed after incubation with atrial natriuretic factor or c(4–23) atrial natriuretic factor. 5. The angiotensin-induced increase in nitric oxide production was not inhibited in the presence of either the angiotensin AT1 or AT2 receptor antagonists DuP 753 or PD 123319. 6. This study demonstrates that primary cultures of human proximal tubular cells can be stimulated to produce nitric oxide by both atrial natriuretic factor and angiotensin II. Furthermore, the atrial natriuretic factor-induced response appears to be mediated via the atrial natriuretic factor-C receptor, while the angiotensin II-induced response appears to be mediated by a novel, as yet unidentified, angiotensin II receptor.

A new biological contribution of cyclo(His-Pro) to the peripheral inhibition of pancreatic secretion

1997 ◽  
Vol 273 (6) ◽  
pp. E1127-E1132 ◽  
Author(s):  
Pascal Fragner ◽  
Olivier Presset ◽  
Nicole Bernad ◽  
Jean Martinez ◽  
Claude Roze ◽  
...  
Keyword(s):  
Pancreatic Secretion ◽  
Biological Activities ◽  
Systemic Circulation ◽  
Inhibitory Effect ◽  
Pancreatic Acinar Cells ◽  
Exocrine Pancreatic Secretion ◽  
Amylase Release ◽  
Pancreatic Acini

The tripeptide pyro-Glu-His-Pro-NH2[thyrotropin-releasing hormone (TRH)] was isolated from the hypothalamus as a thyrotropin-releasing factor. It has a broad spectrum of central nervous system-mediated actions, including the stimulation of exocrine pancreatic secretion. TRH is also synthesized in the endocrine pancreas and found in the systemic circulation. Enzymatic degradation of TRH in vivo produces other bioactive peptides such as cyclo(His-Pro). Because of the short half-life of TRH and the stability of cyclo(His-Pro) in vivo, we postulated that at least part of the peripheral TRH effects on the exocrine pancreatic secretion may be attributed to cyclo(His-Pro), which has been shown to have other biological activities. This study determines in parallel the peripheral effects of TRH and cyclo(His-Pro) as well as the putative contribution of other TRH-related peptides on exocrine pancreatic secretion in rats. TRH and its metabolite cyclo(His-Pro) dose dependently inhibited 2-deoxy-d-glucose (2-DG)-stimulated pancreatic secretion. TRH and all the related peptides tested had no effect on the basal and cholecystokinin-stimulated amylase release from pancreatic acinar cells in vitro. These data indicate that cyclo(His-Pro) mimics the peripheral inhibitory effect of TRH on 2-DG-stimulated exocrine pancreatic secretion. This effect is not detected on isolated pancreatic acini. Our findings provide a new biological contribution for cyclo(His-Pro) with potential experimental and clinical applications.

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 Estimated central blood volume in cirrhosis: Relationship to sympathetic nervous activity, β-adrenergic blockade and atrial natriuretic factor

Hepatology ◽  
1992 ◽  
Vol 16 (5) ◽  
pp. 1163-1170 ◽  
Author(s):  
Jens H. Henriksen ◽  
Flemming Bendtsen ◽  
Alexander L. Gerbes ◽  
Niels Juel Christensen ◽  
Helmer Ring-Larsen ◽  
...  
Keyword(s):  
Blood Volume ◽  
Atrial Natriuretic Factor ◽  
Nervous Activity ◽  
Sympathetic Nervous Activity ◽  
Adrenergic Blockade ◽  
Central Blood Volume ◽  
Natriuretic Factor ◽  
Sympathetic Nervous ◽  
Atrial Natriuretic

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.

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