Human prepro atrial natriuretic factors 26–55, 56–92, and 104–123 increase renal guanylate cyclase activity

Vesely, David L.; Bayliss, J; Sallman, Alan L.

doi:10.1016/0006-291x(87)90648-6

Cited by 52 publications

(20 citation statements)

References 18 publications

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“…35 Previously, in the kidney, physiologically relevant concentrations of this peptide have been shown to act via a guanylyl-cyclase/ cGMP-dependent mechanism and to inhibit renal NKA. 23,29 Clinical data demonstrate that after administration to patients, ppANP exhibits high natriuretic activity but does not significantly affect the arterial pressure. 35 In humans, ␣-hANP lowers the blood pressure 20 but produces a more modest natriuretic effect as compared with that of ppANP.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of the guanylyl cyclase-cGMP-protein kinase G (PKG) pathway underlies both renal and vascular effects of ANP peptides. [23][24][25][26] Because cGMP has been reported to regulate activity of the NKA by modulation of its phosphorylation state, 27,28 we also hypothesized that ANP would affect MBG sensitivity of the NKA via modulation of its PKG-dependent phosphorylation. Previously, ANP has been shown to inhibit renal sodium pump, 25,29,30 and both direct and indirect evidence suggest that ANP and/or cGMP can stimulate the sodium pump in the cardiovascular system.…”

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confidence: 99%

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ANP Differentially Modulates Marinobufagenin-Induced Sodium Pump Inhibition in Kidney and Aorta

et al. 2006

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Abstract-NaCl loading and plasma volume expansion stimulate 2 natriuretic systems, vasoconstrictor, digitalis-like Na/K-ATPase inhibitors and vasorelaxant ANP peptides. Several hormones, including ANP, regulate activity of the Na/K-ATPase by modulation of its phosphorylation state. We studied effects of ANP on Na/K-ATPase phosphorylation and inhibition by an endogenous sodium pump ligand, marinobufagenin, in the aorta and renal medulla from male Sprague-Dawley rats. Marinobufagenin dose-dependently inhibited the Na/K-ATPase in renal and vascular membranes at the level of higher (nanomolar) and lower affinity (micromolar) binding sites. Marinobufagenin (1 nmol/L) inhibited Na/K-ATPase in aortic sarcolemma (18%) and in renal medulla (19%). prepro-ANP 104 to 123 (ppANP) and ␣-human ANP ([␣-hANP] both 1 nmol/L) potentiated marinobufagenin-induced Na/K-ATPase inhibition in the kidney, but reversed the effect of marinobufagenin in the aorta. Similarly, ppANP and ␣-hANP modulated the sodium pump (ouabain-sensitive 86 Rb uptake) inhibitory effects of marinobufagenin in the aorta and renal medulla. In renal medulla, ppANP and ␣-hANP induced ␣-1 Na/K-ATPase phosphorylation, whereas in aorta, both peptides dephosphorylated Na/K-ATPase. The effect of ppANP on Na/K-ATPase phosphorylation and inhibition was mimicked by a protein kinase G activator, 8-Br-PET-cGMP (10 mol/L), and prevented by a protein kinase G inhibitor, KT5823 (60 nmol/L). Our results suggest that ␣-1 Na/K-ATPase inhibition by marinobufagenin in the kidney is enhanced via Na/K-ATPase phosphorylation by ANP, whereas in the aorta, ANP exerts an opposite effect. The concurrent production of a vasorelaxant, ANP, and a vasoconstrictor, marinobufagenin, potentiate each other's natriuretic effects, but ANP peptides may offset the deleterious vasoconstrictor effect of marinobufagenin. Key Words: sodium-potassium exchanging adenosinetriphosphatase Ⅲ natriuretic hormones Ⅲ ANP Ⅲ ouabain Ⅲ marinobufagenin Ⅲ cGMP T he search for the identity of natriuretic factors that become activated under conditions of sodium retention and that promote natriuresis via inhibition of the Na/KATPase (NKA) in the renal tubules evolved from the concept of a natriuretic hormone. [1][2][3][4] According to this concept, in hypertensive patients, excessive response of natriuretic sodium pump ligands produces inhibition of the sodium pump in vascular smooth muscle sarcolemma, potentiating vasoconstriction. 3 Another group of endogenous natriuretics, members of ANP family, are sensitive to NaCl loading and exhibit natriuretic properties, but, unlike digitalis-like factors, natriuretic peptides relax vascular smooth muscle. 5,6 An endogenous bufadienolide NKA inhibitor, marinobufagenin (MBG), is stimulated after acute 7-9 and chronic 10 -12 Na loading, in contrast to endogenous ouabain, which does not exhibit sustained elevations during chronic high NaCl intake 13 but, rather, becomes elevated during sodium restriction. 14 MBG exhibits greater affinity to rodent ouabain-resistant ␣-1 isoform of t...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

ANP Differentially Modulates Marinobufagenin-Induced Sodium Pump Inhibition in Kidney and Aorta

et al. 2006

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“…4.6.1.2).5 Pro-ANF 1-30 and pro-ANF 31-67 also have been found to enhance the guanylate cyclase-cGMP system in the kidney, similar to ANF. 7 The present study details new radioimmunoassays devised to determine if these peptides (pro-ANF 1-30 and pro-ANF 31-67) circulate normally in humans. When the N-terminus (amino acids 1-98) and a 4,000 -MW peptide from the midportion of N-terminus of pro-ANF consistent with pro-ANF 31-67 were found to circulate in 54 normal subjects, this study was extended to determine if the levels of these peptides change in patients with salt and water metabolism abnormalities.…”

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confidence: 99%

The N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of the atrial natriuretic factor prohormone each circulate in humans and increase in congestive heart failure.

Winters¹,

Sallman²,

Baker³

et al. 1989

Circulation

174

141

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Two peptides consisting of amino acids 1-30 and 31-67 of the N-terminus of the prohormone of atrial natriuretic factor (pro-ANF) that have vasodilatory and natriuretic properties were investigated to determine if they circulate in humans. Specific and sensitive radioimmunoassays were developed to amino acids 1-30, 31-67, and 99-126 of pro-ANF. Evaluation of human plasma that had been subjected to reverse-phase high-pressure liquid chromatography suggested that pro-ANFs 1-30 and 31-67 as well as ANF were distinct peaks in human plasma corresponding exactly to pure synthetic peaks of these peptides on high-pressure liquid chromatography. Molecular weight determination of the endogenous immunoreactive peptides measured in plasma by G-50 Sephadex gel permeation chromatography revealed that the pro-ANF 1-30 radioimmunoassay recognized a peptide of 10,000 MW, which is consistent with it measuring the whole N-terminus of pro-ANF (amino acids 1-98) but without ANF (C-terminus) attached to it. The pro-ANF 31-67 radioimmunoassay recognized mainly (more than 95%) a peptide of 3,900-4,000 MW, which corresponds closely with its actual molecular weight of 3,878. Our ANF radioimmunoassay recognizes a peptide in plasma of 3,000 MW with the known molecular weight of ANF being 3,081. The mean circulating concentrations of immunoreactive pro-ANF 1-98, pro-ANF 31-67, and ANF in 54 control subjects were 531±25, 371±+18, and 22±1 fmol/ml (±SEM), respectively. Thirty patients with varying severity of congestive heart failure were also studied. The N-terminus, C-terminus, and pro-ANF 31-67 increased: twofold for New York Heart Association functional Class II, threefold to ninefold for Class III, and 10-to 20-fold for Class IV patients with congestive heart failure. Thus, the N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of pro-ANF as well as ANF circulate normally and increase proportionately to the increasing severity of congestive heart failure. However, because the pro-ANF 31-67 radioimmunoassay was the only assay that discriminated between patients with Class I congestive heart failure and control subjects, this assay may be the most useful to accurately classify the severity of congestive heart failure.

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“…In addition, vessel dilator, long-acting natriuretic peptide and kaliuretic peptide circulate as distinct entities after having been proteolytically cleaved from the rest of the N-terminus by proteases [5,[14][15][16]. Vessel dilator, longacting natriuretic peptide, and ANP bind to specific receptors [17][18][19] and then each of these peptides enhances the particulate form of the enzyme guanylate cyclase (EC 4.6.1.2) as part of their mechanism(s) of action [6,20,21]. The enhancement of guanylate cyclase by each of the respective ANPs increases the intracellular messenger cGMP [6,20,21].…”

Section: Introductionmentioning

confidence: 99%

“…Vessel dilator, longacting natriuretic peptide, and ANP bind to specific receptors [17][18][19] and then each of these peptides enhances the particulate form of the enzyme guanylate cyclase (EC 4.6.1.2) as part of their mechanism(s) of action [6,20,21]. The enhancement of guanylate cyclase by each of the respective ANPs increases the intracellular messenger cGMP [6,20,21]. cGMP has been shown to be a mediator of the observed vasodilation [20] and natriuresis [22] secondary to ANPs.…”

Section: Introductionmentioning

confidence: 99%

Atrial Natriuretic Peptide Increases Urodilatin in the Circulation

Vesely

Overton²,

Blankenship³

et al. 1998

Am J Nephrol

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Background: Urodilatin is a 32-amino-acid (AA) peptide formed in the kidney. Methods: High-performance gel permeation chromatography and high-pressure liquid chromatography evaluation of plasma followed by sensitive urodilatin and atrial natriuretic peptide (ANP) assays revealed that urodilatin does circulate distinctly from ANP. Results: Urodilatin circulates at very low levels (i.e 9–12 pg/ml). Infusion of ANP increased the circulating concentration of urodilatin 135-fold (p < 0.001), suggesting that some of the effects of ANP may be mediated by urodilatin while long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide did not affect urodilatin in healthy humans (n = 30). Only ANP decreased the renal clearance of urodilatin (60–75%, p < 0.01). Urodilatin was metabolized into peptides smaller than 5 AAs as well as excreted intact into urine. Conclusion: Urodilatin circulates and is increased by ANP in humans.

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Human prepro atrial natriuretic factors 26–55, 56–92, and 104–123 increase renal guanylate cyclase activity

Cited by 52 publications

References 18 publications

ANP Differentially Modulates Marinobufagenin-Induced Sodium Pump Inhibition in Kidney and Aorta

ANP Differentially Modulates Marinobufagenin-Induced Sodium Pump Inhibition in Kidney and Aorta

The N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of the atrial natriuretic factor prohormone each circulate in humans and increase in congestive heart failure.

Atrial Natriuretic Peptide Increases Urodilatin in the Circulation

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