scholarly journals The hydrolysis of brain and atrial natriuretic peptides by porcine choroid plexus is attributable to endopeptidase-24.11

1990 ◽  
Vol 271 (2) ◽  
pp. 381-385 ◽  
Author(s):  
A Bourne ◽  
A J Kenny
Keyword(s):  
Choroid Plexus ◽  
Natriuretic Peptide ◽  
Main Product ◽  
Specific Inhibitor ◽  
Atrial Natriuretic Peptides ◽  
Initial Product ◽  
Prolonged Incubation ◽  
Endopeptidase 24.11 ◽  
Hydrolysis Of ◽  
Atrial Natriuretic

The hydrolysis of the porcine 26-residue brain natriuretic peptide (BNP-26) and its counterpart human 28-residue atrial natriuretic peptide (alpha-hANP) by pig membrane preparations and purified membrane peptidases was studied. When the two peptides were incubated with choroid plexus membranes, the products being analysed by h.p.l.c., alpha-hANP was degraded twice as fast as BNP. The h.p.l.c. profiles of alpha-hANP hydrolysis, in short incubations with choroid plexus membranes, yielded alpha hANP′ as the main product, this having been previously shown to be the result of hydrolysis at the Cys7-Phe8 bond. In short incubations this cleavage was inhibited 84% by 1 microM-phosphoramidon, a specific inhibitor of endopeptidase-24.11. BNP-26 was hydrolysed by choroid plexus membranes, kidney microvillar membranes and purified endopeptidase-24.11 in a manner that yielded identical h.p.l.c. profiles. In the presence of phosphoramidon, hydrolysis by the choroid plexus membranes was 94% inhibited. Captopril had no effect and, indeed, no hydrolysis of BNP-26 by peptidyl dipeptidase A (angiotensin-converting enzyme) was observed even after prolonged incubation with the purified enzyme. The stepwise hydrolysis of BNP-26 by endopeptidase-24.11 was investigated by sequencing the peptides produced during incubation. The initial product resulted from hydrolysis at Ser14-Leu15, thereby opening the ring. This product (BNP′) was short-lived; further degradation involved hydrolysis at Ile12-Gly13, Arg8-Leu9, Gly17-Leu18, Val22-Leu23, Arg11-Ile12 and Cys4-Phe5. Thus endopeptidase-24.11 is the principal enzyme in renal microvillar and choroid plexus membranes hydrolysing BNP-26 and alpha-hANP.

scholarly journals Hydrolysis of human and pig brain natriuretic peptides, urodilatin, C-type natriuretic peptide and some C-receptor ligands by endopeptidase-24.11

1993 ◽  
Vol 291 (1) ◽  
pp. 83-88 ◽  
Author(s):  
A J Kenny ◽  
A Bourne ◽  
J Ingram
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Receptor Ligands ◽  
Prolonged Incubation ◽  
Endopeptidase 24.11 ◽  
Pig Brain ◽  
Hydrolysis Of ◽  
Atrial Natriuretic

Endopeptidase-24.11 (E-24.11, EC 3.4.24.11) is widely believed to play a physiological role in metabolizing atrial natriuretic peptide (ANP). Since the discovery of ANP, new natriuretic peptides have been isolated and other peptides synthesized as receptor ligands. The hydrolysis in vitro of six related peptides by the endopeptidase has been studied, mainly by h.p.l.c. The initial attack on the 32-residue form of pig brain natriuretic peptide (pBNP-32) was shown to be at the Ser20-Leu21 bond, as had been previously shown for the 26-residue form. In contrast, human brain natriuretic peptide-32 (hBNP-32), which differs in ten residues from pBNP-32, was attacked first at the Met4-Val5 bond, releasing the N-terminal tetrapeptide, and only later at bonds within the ring: at Arg17-Ile18 and subsequently at four other sites. Urodilatin, which has a four-residue extension at the N-terminus compared with alpha-human atrial natriuretic peptide-28 (alpha-hANP), was degraded at about half the rate of the latter, though the C-terminal Phe-Arg-Tyr was released at the same rate. The 22-residue C-type natriuretic peptide was hydrolysed more rapidly than alpha-hANP, as were two C-receptor ligands (peptides with deletions within the ring): C-ANP4-23 (rANP4-23 des-Gln18,Ser19,Gly20,Leu21,Gly22) and SC 46542 (hANP5-28 des-Phe8,Gly9,Ala17,Gln18). Angiotensin-converting enzyme failed to hydrolyse pBNP-32, hBNP-32 or 125I-rat (r) ANP, even after prolonged incubation. Km and kcat values were determined for the hydrolysis of alpha-hANP, porcine BNP-26, porcine BNP-32 and 125I-rANP by E-24.11. Ki values were determined for six peptides, alpha-hANP, urodilatin, hBNP-32, C-type natriuretic peptide (CNP), SC 46542 and C-type natriuretic peptide (C-ANP4-23), in radiometric assays of E-24.11 with either [125I] insulin B chain or [125I] rANP as substrate. The Ki values (2.5-13 microM) for CNP were the lowest of any of the group, whereas those for hBNP-32 (151-172 microM) were the highest. The physiological significance of these results is discussed, especially in regard to the relative resistance of hBNP-32 to attack and the ability of the C-receptor ligands to compete with natriuretic peptides for hydrolysis by E-24.11.

scholarly journals The hydrolysis of α-human atrial natriuretic peptide by pig kidney microvillar membranes is initiated by endopeptidase-24.11

1987 ◽  
Vol 243 (1) ◽  
pp. 183-187 ◽  
Author(s):  
S L Stephenson ◽  
A J Kenny
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Angiotensin I ◽  
Human Atrial Natriuretic Peptide ◽  
Pig Kidney ◽  
Angiotensin I Converting Enzyme ◽  
Endopeptidase 24.11 ◽  
Hydrolysis Of ◽  
Atrial Natriuretic

alpha-Human atrial natriuretic peptide, a 28-amino-acid-residue peptide, was rapidly hydrolysed by pig kidney microvillar membranes in vitro, with a t1/2 of 8 min, comparable with the rate observed with angiotensins II and III. The products of hydrolysis were analysed by h.p.l.c., the pattern obtained with membranes being similar to that with purified endopeptidase-24.11 (EC 3.4.24.11). No hydrolysis by peptidyl dipeptidase A (angiotensin I converting enzyme, EC 3.4.15.1) was observed. The contribution of the various microvillar membrane peptidases was assessed by including specific inhibitors. Phosphoramidon, an inhibitor of endopeptidase-24.11, caused 80-100% suppression of the products. Captopril and amastatin (inhibitors of peptidyl dipeptidase A and aminopeptidases respectively) had no significant effect. Hydrolysis at an undefined site within the disulphide-linked ring occurred rapidly, followed by hydrolysis at other sites, including the Ser25--Phe26 bond.

Increased levels of brain and atrial natriuretic peptides after the first palliative operation, but not after a bidirectional Glenn anastomosis, in children with functionally univentricular hearts

2003 ◽  
Vol 13 (3) ◽  
pp. 268-274 ◽  
Author(s):  
Håkan Wåhlander ◽  
Andreas Westerlind ◽  
Göran Lindstedt ◽  
Per-Arne Lundberg ◽  
Daniel Holmgren
Keyword(s):  
Ventricular Function ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Heart Defects ◽  
Control Group ◽  
Atrial Natriuretic Peptides ◽  
Palliative Operation ◽  
Bidirectional Glenn ◽  
The Brain ◽  
Atrial Natriuretic

We evaluated the concentrations of the brain and atrial natriuretic peptides in the plasma as markers of ventricular function and volume load in children with functionally univentricular hearts. We studied 7 children aged from 0.5 to 0.7 years with functionally univentricular hearts who had undergone a first palliative operation, and 10 children aged from 1.8 to 3.7 years who had undergone a bidirectional Glenn anastomosis at ages ranging from 0.4 to 1.0 year. As a control group, we studied 14 children without heart defects aged from 0.1 to 4.5 years. Levels of the brain natriuretic peptide were measured at 8.3 to 122 ng/l, with a mean of 52.8 ng/l, after the first palliative operation, compared to 0 to 16 ng/l, with a mean of 7.3 ng/l, after a bidirectional Glenn anastomosis, and 0 to 13.8 ng/l, with a mean of 5.9 ng/l, in the children serving as controls. Corresponding values for atrial natriuretic peptide were 17 to 203 ng/l, with a mean of 103 ng/l, after the first palliative operation, compared to 16 to 54 ng/l, with a mean of 29 ng/l, after the bidirectional Glenn anastomosis, and 12 to 52 ng/l, with a mean of 32 ng/l in the controls. Echocardiography showed that all the children with functionally univentricular hearts had normal ventricular function. Blood presssure, pulmonary arterial pressure, and arterial saturations of oxygen did not differ between the groups. We conclude, that in children with functionally univentricular hearts, the volume overload imposed on the heart after the first palliative operation is associated with increased production of brain and atrial natriuretic peptides, while after ventricular unloading, levels of the natriuretic peptides return to control values.

Chronic inhibition of endopeptidase 24.11 in essential hypertension: evidence for enhanced atrial natriuretic peptide and angiotensin II

1993 ◽  
Vol 11 (4) ◽  
pp. 407-416 ◽  
Author(s):  
A Mark Richards ◽  
Gary A. Wittert ◽  
Ian G. Crozier ◽  
Eric A. Espiner ◽  
Timothy G. Yandle ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Angiotensin Ii ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Endopeptidase 24.11 ◽  
Atrial Natriuretic

Atrial natriuretic peptide inhibits cell cycle activity of embryonic cardiac progenitor cells via its NPRA receptor signaling axis

2015 ◽  
Vol 308 (7) ◽  
pp. C557-C569 ◽  
Author(s):  
Adam Hotchkiss ◽  
Tiam Feridooni ◽  
Mark Baguma-Nibasheka ◽  
Kathleen McNeil ◽  
Sarita Chinni ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Progenitor Cells ◽  
Natriuretic Peptide ◽  
Biological Effects ◽  
Active Form ◽  
Specific Inhibitor ◽  
Ventricular Myocardium ◽  
Biologically Active ◽  
Cardiac Progenitor Cells ◽  
Atrial Natriuretic

The biological effects of atrial natriuretic peptide (ANP) are mediated by natriuretic peptide receptors (NPRs), which can either activate guanylyl cyclase (NPRA and NPRB) or inhibit adenylyl cyclase (NPRC) to modulate intracellular cGMP or cAMP, respectively. During cardiac development, ANP serves as an early maker of differentiating atrial and ventricular chamber myocardium. As development proceeds, expression of ANP persists in the atria but declines in the ventricles. Currently, it is not known whether ANP is secreted or the ANP-NPR signaling system plays any active role in the developing ventricles. Thus the primary aims of this study were to 1) examine biological activity of ANP signaling systems in embryonic ventricular myocardium, and 2) determine whether ANP signaling modulates proliferation/differentiation of undifferentiated cardiac progenitor cells (CPCs) and/or cardiomyocytes. Here, we provide evidence that ANP synthesized in embryonic day (E)11.5 ventricular myocytes is actively secreted and processed to its biologically active form. Notably, NPRA and NPRC were detected in E11.5 ventricles and exogenous ANP stimulated production of cGMP in ventricular cell cultures. Furthermore, we showed that exogenous ANP significantly decreased cell number and DNA synthesis of CPCs but not cardiomyocytes and this effect could be reversed by pretreatment with the NPRA receptor-specific inhibitor A71915. ANP treatment also led to a robust increase in nuclear p27 levels in CPCs compared with cardiomyocytes. Collectively, these data provide evidence that in the developing mammalian ventricles ANP plays a local paracrine role in regulating the balance between CPC proliferation and differentiation via NPRA/cGMP-mediated signaling pathways.

C-type natriuretic peptide and atrial natriuretic peptide receptors of rat brain

1993 ◽  
Vol 264 (3) ◽  
pp. R513-R523 ◽  
Author(s):  
J. Brown ◽  
Z. Zuo
Keyword(s):  
Olfactory Bulb ◽  
Atrial Natriuretic Peptide ◽  
Rat Brain ◽  
Choroid Plexus ◽  
Natriuretic Peptide ◽  
Binding Sites ◽  
Specific Binding ◽  
Peptide Receptors ◽  
Natriuretic Peptide Receptors ◽  
Atrial Natriuretic

Natriuretic peptide receptors in rat brain were mapped by in vitro autoradiography using 125I-labeled [Tyr0]CNP-(1-22) to bind atrial natriuretic peptide receptor (ANPR)-B and ANPR-C receptors selectively, and 125I-labeled alpha-ANP to select ANPR-A and ANPR-C receptors. Des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4- 23)-amide (C-ANP) was used for its selectivity for ANPR-C over ANPR-A. Specific binding of 125I-[Tyr0]CNP-(1-22) with a dissociation constant (Kd) approximately 1 nM occurred in olfactory bulb, cerebral cortex, lateral septal nucleus, choroid plexus, and arachnoid mater. This binding was abolished by C-type natriuretic peptide [CNP-(1-22)], alpha-ANP and C-ANP, and conformed to ANPR-C. 125I-alpha-ANP bound to all structures that bound 125I-[Tyr0]CNP-(1-22). This binding was also inhibited by both CNP-(1-22) and C-ANP, confirming the presence of ANPR-C-like binding sites. However, ANPR-C-like binding sites were heterogenous because only some had high affinities for 125I-[Tyr0]CNP-(1-22) and CNP-(1-22). 125I-alpha-ANP also bound sites without affinities for C-ANP or CNP-(1-22). These sites were consistent with ANPR-A. They occurred mainly on the olfactory bulb, the choroid plexus, and the subfornical organ. Guanosine 3',5'-cyclic monophosphate production was strongly stimulated by alpha-ANP but not by CNP-(1-22) in olfactory bulb. Neither ligand stimulated it in cortical tissue. Thus the natriuretic peptide binding sites of rat brain conformed to ANPR-A and to heterogenous ANPR-C-like sites. No ANPR-B were detected.

Changes in the plasma levels of atrial natriuretic peptides during mineralocorticoid escape in man

1987 ◽  
Vol 72 (5) ◽  
pp. 531-539 ◽  
Author(s):  
Francesco P. Cappuccio ◽  
Nirmala D. Markandu ◽  
Martin G. Buckley ◽  
Giuseppe A. Sagnella ◽  
Angela C. Shore ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Healthy Volunteers ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Plasma Levels ◽  
Sodium Intake ◽  
Atrial Natriuretic Peptides ◽  
Atrial Natriuretic

1. Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay in eight normal healthy volunteers before and during mineralocorticoid escape. 2. Mean plasma ANP on a fixed sodium intake before fludrocortisone was 6.5± sem 1.1 pg/ml. Within 24 h of fludrocortisone administration there was a significant increase in plasma ANP which continued to increase daily reaching a plateau by day 4 (14.9 ± 2.4 pg/ml) to day 7 (15.1 ± 2.6 pg/ml). 3. The rise in plasma ANP was closely related to the amount of sodium retained during the fludrocortisone treatment and the sodium ‘escape’ occurred by days 4 to 7. 4. These results support the concept that ANP could play an important hormonal role in overcoming the sodium-retaining effects of mineralocorticoids in man.

Sign in / Sign up

Export Citation Format

Share Document