Atrial natriuretic peptide (ANP) is a high-affinity substrate for rat insulin-degrading enzyme

1. In the presence of calcium, both high- [dissociation equilibrium constant (Kd) 5.8 × 10−11 mol/l] and low-(Kd 1.2 × 10−8 mol/l) affinity binding of atrial natriuretic peptide was detected on plasma membranes prepared from sodium-depleted rats. 2. In contrast, under calcium-free conditions only high-affinity binding (Kd 6.9 × 10−11 mol/l) was detected. 3. The requirement for calcium for low-affinity binding suggests a different mechanism of action than that for the high-affinity receptor.

Download Full-text

Specific binding of atrial natriuretic peptide to rat mesenteric artery: Effect of calcium and 5-guanylylimidodiphosphate

Clinical Science ◽

10.1042/cs0730573 ◽

1987 ◽

Vol 73 (6) ◽

pp. 573-579 ◽

Cited By ~ 9

Author(s):

Fiona Lyall ◽

J. J. Morton

Keyword(s):

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Binding Sites ◽

Mesenteric Artery ◽

Guanosine Triphosphate ◽

High Affinity ◽

Dissociation Equilibrium ◽

Rat Mesenteric Artery ◽

Receptor Number ◽

Atrial Natriuretic

1. High-dissociation equilibrium constant (20 pmol/l, receptor number 17 fmol/mg) and low-dissociation equilibrium constant (10 nmol/l, receptor number 5 nmol/mg) affinity binding sites for atrial natriuretic peptide have been identified in membrane preparations from rat mesenteric artery. 2. Tracer degradation was corrected for mathematically and binding data were analysed by a non-linear computer technique. 3. Non-atrial natriuretic peptide vasoactive hormones, angiotensin II, vasopressin and bradykinin, did not compete for the high-affinity site. Related peptides with either C- or N-terminal amino acids missing still competed, while peptides without an intact disulphide bridge did not compete. 4. Neither the addition nor the removal of calcium affected the affinity or density of binding sites. Also the non-hydrolysable guanosine triphosphate analogue 5-guanylylimidodiphosphate had no effect on either affinity or number of sites. 5. These results indicate the presence of a specific high-affinity vascular receptor for atrial natriuretic peptide which could interact with the hormone under physiological conditions. The mechanism of binding is uncertain but is unlikely to involve calcium- or guanosine triphosphate-associated regulatory sites.

Download Full-text

Competitive binding of musclin to natriuretic peptide receptor 3 with atrial natriuretic peptide

Journal of Endocrinology ◽

10.1677/joe-08-0551 ◽

2009 ◽

Vol 201 (2) ◽

pp. 287-295 ◽

Cited By ~ 15

Author(s):

Shunbun Kita ◽

Hitoshi Nishizawa ◽

Yosuke Okuno ◽

Masaki Tanaka ◽

Atsutaka Yasui ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Homologous Region ◽

Binding Assays ◽

Peptide Receptor ◽

High Affinity ◽

Clearance Receptor ◽

Competitive Nature ◽

Atrial Natriuretic

Musclin is a novel skeletal muscle-derived secretory factor that was isolated by our group. Musclin contains a region homologous to natriuretic peptides (NPs). This study investigated the interaction between musclin and NP receptors (NPRs). Musclin specifically bound to NPR3, but not to NPR1 or NPR2. Musclin and atrial natriuretic peptide (ANP) competed for binding to NPR3. We conducted binding assays using various synthetic musclin peptides and mutant musclin proteins. The first NP-homologous region in musclin (88LDRL91) and the second homologous region (117MDRI120) were responsible cooperatively for high-affinity binding to NPR3. The first NP-homologous region was more importantly associated with binding to NPR3, than the second homologous region. The competitive nature of musclin with ANP for the natriuretic clearance receptor NPR3 was also confirmed in vivo. We conclude that musclin binds to NPR3 competitively with ANP and may affect ANP concentrations in a local or systemic manner.

Download Full-text

Specific endothelin binding sites in renal medullary collecting duct cells: lack of interaction with ANP binding and cGMP signalling

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y92-162 ◽

1992 ◽

Vol 70 (8) ◽

pp. 1167-1174 ◽

Cited By ~ 14

Author(s):

Peter Cernacek ◽

Louis Legault ◽

Duncan J. Stewart ◽

Mortimer Levy

Keyword(s):

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Binding Sites ◽

Collecting Duct ◽

Specific Cell ◽

Binding Studies ◽

Single Class ◽

High Affinity ◽

Medullary Collecting Duct ◽

Atrial Natriuretic

The diverse biological actions of endothelins (ET) appear to be mediated by specific cell-surface receptors. Autoradiography and membrane binding studies have shown abundant ET binding sites in the kidney. However, their expression in specific types of renal cells is unclear. We studied the binding of 125I-labelled endothelin-1 in freshly isolated cell suspensions from canine inner medullary collecting duct. Competition binding experiments revealed the presence of specific high-affinity binding sites: unlabelled ET-1 and ET-2 competed with the radioligand with an IC50 of 135 and 83 pM, respectively, while the IC50 of ET-3 and big ET-1 were 2 and 4 orders of magnitude higher, indicating the presence of ETA-type receptor. Angiotensin II, vasopressin, and atrial natriuretic peptide (ANP) did not compete for ET binding even at a concentration of 10−6 M. Saturation binding experiments showed a single class of binding sites of high density (Bmax = 56.7 ± 10.3 fmol/106 cells) and high affinity (Kd = 69.8 ± 10 pM). In contrast, ANP receptors in the same cell preparations appeared as two classes of binding sites with widely different affinity and density. The high-affinity ANP site (Kd = 311 ± 48 pM) was compatible with ANP-B (guanylate cyclase-coupled) receptor. ET-1 did not compete for this receptor. ET-1 (10−7 M) did not alter ANP-induced cGMP generation in these cells (3.8-fold increase at 10−7 M ANP), nor basal levels of cGMP. The expression by the distal tubular epithelium of specific ET-1 binding sites strongly suggests the presence of a functional receptor, which may mediate the inhibition of Na+ transport in these cells. The mechanism and the transduction pathway of this effect appear to be different and independent from those of ANP.Key words: endothelin receptor, distal collecting duct, atrial natriuretic peptide receptor, cGMP generation.

Download Full-text

Dopamine D1 antagonist inhibits natriuretic response of α-rat atrial natriuretic peptide(1-28)(α-rANP) by interacting with specific, high affinity dopamine D1-like receptors in the outer cortex of rat kidney

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)57756-3 ◽

1988 ◽

Vol 46 ◽

pp. 305

Author(s):

Tetsu Maeda ◽

Masami Niwa ◽

Kazuto Shigematsu ◽

Tatsunobu Ohkubo ◽

Kimihiro Yamashita ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Rat Kidney ◽

Outer Cortex ◽

High Affinity ◽

Dopamine D1 Antagonist ◽

Atrial Natriuretic

Download Full-text

Renal atrial natriuretic peptide receptor subtypes in spontaneously hypertensive rats

AJP Renal Physiology ◽

10.1152/ajprenal.1990.259.4.f605 ◽

1990 ◽

Vol 259 (4) ◽

pp. F605-F612

Author(s):

J. Brown ◽

S. P. Salas ◽

J. M. Polak

Keyword(s):

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Spontaneously Hypertensive Rats ◽

Receptor Subtypes ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Reversible Binding ◽

High Affinity ◽

Wistar Kyoto ◽

Atrial Natriuretic

Receptor subtypes for atrial natriuretic peptide (ANP) were characterized in kidneys of 18-wk-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) by in vitro autoradiography through use of des[Gln18, Ser19, Gly20, Leu21, Gly22] ANP-(4–23) (C-ANP) and ANP-(5–25) as subtype-selective ligands. alpha-125I-ANP (100 pM) bound reversibly but with high affinity to glomeruli, to stripes in outer medulla, and to inner medulla of both WKY and SHR. C-ANP (10 microM) inhibited approximately 70% of the glomerular binding but none of the medullary binding in either strain. All high-affinity specifically reversible binding sites for alpha-ANP that bound C-ANP were also bound by 10 microM ANP-(5–25). However, the specifically reversible binding of alpha-125I-ANP that was not inhibited by 10 microM C-ANP behaved differently in each strain. In WKY, this binding was weakly inhibited by ANP-(5–25), so that even the presence of 10 microM ANP-(5–25) did not inhibit some glomerular binding and greater than 40% of the specifically reversible medullary binding of alpha-125I-ANP. In SHR, this binding was inhibited by ANP-(5–25) with a significantly higher affinity so that all specifically reversible binding of alpha-125I-ANP was inhibited by 10 microM ANP-(5–25). SHR also showed higher affinities but lower maximum binding capacities for alpha-ANP in their outer cortical glomeruli and medullas. These results suggest that the preponderant medullary ANP receptor differs between WKY and SHR. Differences in glomerular subtypes of ANP receptor may also distinguish WKY and SHR.

Download Full-text