Adenine nucleotides decrease the apparentKmof endogenous natriuretic peptide receptors for GTP

2007 ◽  
Vol 293 (6) ◽  
pp. E1756-E1763 ◽  
Author(s):  
Laura K. Antos ◽  
Lincoln R. Potter
Keyword(s):  
Natriuretic Peptide ◽  
Adenine Nucleotides ◽  
Cyclase Activity ◽  
Wild Type ◽  
Peptide Receptors ◽  
Natriuretic Peptide Receptors ◽  
Independent Mechanism ◽  
Initial Activation ◽  
Type Receptor ◽  
Guanylyl Cyclase Activity

Natriuretic peptide receptors A (NPR-A) and B (NPR-B) mediate most effects of natriuretic peptides by synthesizing cGMP. ATP increases the activity of these receptors by an unknown mechanism. We recently reported that a nonhydrolyzable form of ATP, adenylyl imidodiphosphate (AMPPNP), stabilizes but is not required for the activation of NPR-A and NPR-B in membranes from highly overexpressing cells. Here, we repeated these studies on receptors expressed in endogenous settings. Kinetic analysis indicated that both AMPPNP and ATP dramatically decrease the apparent Kmof both receptors for GTP but had little effect on the Vmax. The EC50for AMPPNP decreased as substrate concentration increased whereas the magnitude of the effect was greater at lower GTP concentrations. ATP increased the activity of a mutant receptor containing glutamates substituted for all known phosphorylation sites similarly to the wild-type receptor, consistent with a phosphorylation independent mechanism. Finally, the putative ATP binding sites were investigated. Mutation of the ATP modulatory domain region had no effect, but mutation of K535A dramatically diminished ANP-dependent cyclase activity in a manner that was unresponsive to ATP. Mutation of the highly conserved 630-KSS to AAA (all alanines) resulted in an expressed receptor that had no detectable guanylyl cyclase activity. We conclude that ATP is not required for the initial activation of NPRs but does increase activity over time by reducing the apparent Kmfor GTP.

Gene expression of natriuretic peptide receptors in rats with DOCA-salt hypertension

1997 ◽  
Vol 273 (4) ◽  
pp. C1427-C1434 ◽  
Author(s):  
Edem Nuglozeh ◽  
Majambu Mbikay ◽  
Duncan J. Stewart ◽  
Louis Legault
Keyword(s):  
Adrenal Cortex ◽  
Natriuretic Peptide ◽  
Mesenteric Arteries ◽  
Peptide Receptors ◽  
Natriuretic Peptide Receptors ◽  
Its Gene ◽  
Salt Hypertension ◽  
Steady State Levels ◽  
And Control ◽  
Guanylyl Cyclase Activity

In our previous studies, we found that the atrial natriuretic peptide (ANP) binding and guanylyl cyclase activity of A-type natriuretic peptide receptors (NPR-A) were upregulated in renal papillae but downregulated in vascular tissues and glomeruli of rats with deoxycorticosterone acetate (DOCA)-salt hypertension [E. Nuglozeh, G. Gauquelin, R. Garcia, J. Tremblay, and E. L. Schiffrin. Am. J. Physiol. 259 ( Renal Fluid Electrolyte Physiol. 28): F130–F137, 1990]. To further understand the molecular significance of these regulations, we measured the relative abundance of the transcripts of NPR-A and NPR-B by Northern blot in the aorta, mesenteric arteries, adrenal cortex, renal papillae, and lungs in DOCA-salt hypertensive and control rats. In renal papillae we also examined the translation and transcription of NPR-A by ribosome loading and run-on assay. Compared with controls, the steady-state levels of mRNA for NPR-A were increased in the aorta and mesenteric arteries but were decreased in the adrenal cortex and renal papillae in DOCA-salt-treated rats. NPR-B mRNA was decreased in the aorta, mesenteric arteries, and adrenal cortex in hypertensive rats. In lungs the mRNA for both receptors was unchanged. Translation of NPR-A mRNA, as assessed by ribosome loading, was reduced in renal papillae. Transcriptional activity of its gene was not detectable in these tissues. Guanosine 3′,5′-cyclic monophosphate levels generated by NPR-A in renal papillae and by NPR-A and NPR-B in the adrenal cortex, aorta, and mesenteric arteries of DOCA-salt-treated rats remained increased in hypertension. The higher NPR-A activity in the presence of a lower level of its mRNA in renal papillae and the higher NPR-B activity in the presence of a lower level of its mRNA in the vasculature, adrenal cortex, and lungs can alternatively be explained by receptor stabilization or increased receptor recycling.

scholarly journals Augmented Natriuretic Peptide-Induced Guanylyl Cyclase Activity and Vasodilation in Experimental Hyperglycemic Rats

2002 ◽  
Vol 88 (2) ◽  
pp. 167-173 ◽  
Author(s):  
Hyun Kook ◽  
JongUn Lee ◽  
Soo Wan Kim ◽  
Sang Woo Kim ◽  
Yung Hong Baik
Keyword(s):  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Cyclase Activity ◽  
Guanylyl Cyclase Activity

scholarly journals ATP-independent activation of natriuretic peptide receptors

2005 ◽  
Vol 5 (Suppl 1) ◽  
pp. P3
Author(s):  
Laura K Antos ◽  
Sarah E Abbey-Hosch ◽  
Darcy R Flora ◽  
Lincoln R Potter
Keyword(s):  
Natriuretic Peptide ◽  
Peptide Receptors ◽  
Natriuretic Peptide Receptors

scholarly journals Natriuretic peptide receptors in the kidney and the ventral and dorsal aortae of the Atlantic hagfish Myxine glutinosa (Agnatha).

1995 ◽  
Vol 198 (9) ◽  
pp. 1875-1882 ◽  
Author(s):  
T Toop ◽  
J A Donald ◽  
D H Evans
Keyword(s):  
Natriuretic Peptide ◽  
Binding Sites ◽  
Kidney Tissue ◽  
Peptide Receptors ◽  
Natriuretic Peptide Receptors ◽  
Myxine Glutinosa ◽  
Clearance Receptor ◽  
Relationship Of ◽  
The Relationship ◽  
Gmp Production

The character of natriuretic peptide receptors (NPRs) in the kidney and aortae of the Atlantic hagfish Myxine glutinosa was determined and compared with that of NPRs in hagfish gills. The relationship of hagfish kidney and aortic NPRs with NPRs from higher vertebrates was also examined. Iodinated atrial and C-type natriuretic peptides (NPs) (125I-ANP, 125I-CNP) were used in tissue section autoradiography, competition studies and guanylate cyclase (GC) assays. Rat atrial and porcine C-type NPs (rANP, pCNP) and rat des[Gln18, Ser19, Gly20, Leu21 Gly22]ANP-(4-23)-NH2 (C-ANF, which binds to the mammalian and teleost 'clearance' receptor, NPR-C), were used as competing ligands. 125I-ANP binding sites were observed on both aortae and on the glomeruli, neck segments and archinephric ducts of the kidney. 4.0 nmol l-1 rANP competed for 50% of 125I-ANP glomerular sites. 125I-CNP did not visibly bind to any of the tissues, but 300 nmol l-1 pCNP competed for 50% of 125I-ANP glomerular sites. C-ANF failed to compete for 125I-ANP sites. rANP and pCNP stimulated cyclic GMP production in kidney membrane preparations, but C-ANF did not, demonstrating that the hagfish kidney NPR is GC-linked. This study suggests that a predominant population of ANP-like receptors, similar to the mammalian NPR-A, exists in the myxinoid aortae and kidney tissue. However, no detectable population of a receptor that binds all NPs, such as is present in the hagfish gill, nor an NPR similar to the NPR-C of higher vertebrates was discovered.

Conservation of the kinaselike regulatory domain is essential for activation of the natriuretic peptide receptor guanylyl cyclases

1992 ◽  
Vol 12 (6) ◽  
pp. 2581-2590
Author(s):  
K J Koller ◽  
F J de Sauvage ◽  
D G Lowe ◽  
D V Goeddel
Keyword(s):  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Cyclase Activity ◽  
Guanylyl Cyclases ◽  
Heat Stable ◽  
Guanylyl Cyclase Activity ◽  
Kinase Homology Domain ◽  
Kinase Homology

The natriuretic peptide receptors, NPR-A and NPR-B, are two members of the newly described class of receptor guanylyl cyclases. The kinaselike domain of these proteins is an important regulator of the guanylyl cyclase activity. To begin to understand the molecular nature of this type of regulation, we made complete and partial deletions of the kinase domain in NPR-A and NPR-B. We also made chimeric proteins in which the kinase domains of NPR-A and NPR-B were exchanged or replaced with kinase domains from structurally similar proteins. Complete deletion of the kinase homology domain in NPR-A and NPR-B resulted in constitutive activation of the guanylyl cyclase. Various partial deletions of this region produced proteins that had no ability to activate the enzyme with or without hormone stimulation. The kinase homology domain can be exchanged between the two subtypes with no effect on regulation. However, structurally similar kinaselike domains, such as from the epidermal growth factor receptor or from the heat-stable enterotoxin receptor, another member of the receptor guanylyl cyclase family, were not able to regulate the guanylyl cyclase activity correctly. These findings suggest that the kinaselike domain of NPR-A and NPR-B requires strict sequence conservation to maintain proper regulation of their guanylyl cyclase activity.

Localization and analysis of natriuretic peptide receptors in the gills of the toadfish, Opsanus beta (teleostei)

1994 ◽  
Vol 267 (6) ◽  
pp. R1437-R1444 ◽  
Author(s):  
J. A. Donald ◽  
T. Toop ◽  
D. H. Evans
Keyword(s):  
Natriuretic Peptide ◽  
Binding Sites ◽  
Peptide Receptors ◽  
Natriuretic Peptide Receptors ◽  
Major Band ◽  
Opsanus Beta ◽  
Secondary Lamellae ◽  
Membrane Bound ◽  
Type C ◽  
Specific Ligand

The distribution and nature of natriuretic peptide binding sites was determined in the gills of the toadfish, Opsanus beta. Specific 125I-labeled rat atrial natriuretic peptide (rANP) and 125I-labeled porcine C-type natriuretic peptide (pCNP) binding sites were observed on the afferent and efferent filamental arteries and lamellar arterioles, and on the marginal channels of the secondary lamellae. In both section autoradiography and competition assays, the binding of both ligands was completely displaced by 1 microM rANP and 1 microM pCNP, but residual binding was observed with 1 microM of the type C natriuretic peptide receptor (NPR-C)-specific ligand C-ANF. Electrophoresis of gill membranes cross-linked with 125I-rANP showed a major band at 75 kDa and a fainter band at 140 kDa. Both rANP and pCNP significantly stimulated the production of cGMP above basal levels; C-ANF had no stimulatory effect. These data show that the intrafilamental gill vasculature of toadfish contains a major population of natriuretic peptide receptors very similar to mammalian clearance receptors and a smaller population of receptors that are linked to a membrane-bound guanylate cyclase.

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