Natriuretic peptide receptor-C releases and activates guanine nucleotide-exchange factor H1 in a ligand-dependent manner

Nishida, Mika; Miyamoto, K.; Abe, Shogo; Shimada, Mistuo; Shimizu, Yuki; Tsuji, Akihiko; Yuasa, Keizo

doi:10.1016/j.bbrc.2021.03.028

Cited by 4 publications

(5 citation statements)

References 24 publications

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“…2 ). OSTN binds to its physiological receptor NPR-1 through two oligopeptides (NM1 and NM2) with similar sequences to the binding regions of ANP, BNP, and CNP [ 41 , 64 ] ( Supplementary Fig. 3 ).…”

Section: Resultsmentioning

confidence: 99%

The natriuretic peptide receptor agonist osteocrin disperses Pseudomonas aeruginosa biofilm

Louis¹,

Tahrioui²,

Lendon

et al. 2023

Biofilm

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Section: Resultsmentioning

confidence: 99%

The natriuretic peptide receptor agonist osteocrin disperses Pseudomonas aeruginosa biofilm

Louis¹,

Tahrioui²,

Lendon

et al. 2023

Biofilm

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“…Notably, in the present study, plasma levels of all three NPs remained elevated for a sustained period after cessation of OSTN (see Figure 3 ), in keeping with a sustained reduction in NPR‐C capacity. Presumably, like bioactive NPs, OSTN is initially bound to NPR‐C, then internalized to interact with GEF‐H1 (a guanine nucleotide exchange factor) (Nishida et al., 2021 ). Furthermore, the barely detectable level of OSTN in the resting (basal) state, when plasma ANP concentration is ∼12–15 pmol/L, suggests that physiological levels of NPs have little or no impact on the OSTN concentration.…”

Section: Discussionmentioning

confidence: 99%

“…Collectively, these studies suggest that OSTN might be an endogenous ligand for NPR-C capable of regulating plasma concentrations of the NPs, in addition to local bioavailability and activity in tissues targeted by the NPs. Although the physiological effects of OSTN have been ascribed largely to reduced NPR-C-dependent NP clearance, there is some evidence of direct biological activity mediated by this receptor (via G i -inhibitory/regulatory proteins and several intracellular signalling pathways, including adenylyl cyclase/cAMP signal transduction; Anand-Srivastava, 2005;Nishida et al, 2021), including cardiovascular effects (Moyes et al, 2020) and renal tubular sodium reabsorption (Shao et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…Although the physiological effects of OSTN have been ascribed largely to reduced NPR‐C‐dependent NP clearance, there is some evidence of direct biological activity mediated by this receptor (via G i ‐inhibitory/regulatory proteins and several intracellular signalling pathways, including adenylyl cyclase/cAMP signal transduction; Anand‐Srivastava, 2005 ; Nishida et al. , 2021 ), including cardiovascular effects (Moyes et al. , 2020 ) and renal tubular sodium reabsorption (Shao et al.…”

Section: Introductionmentioning

confidence: 99%

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Haemodynamic, hormonal and renal actions of osteocrin in normal sheep

Scott,

Prickett,

Charles

et al. 2024

Experimental Physiology

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Osteocrin (OSTN) is an endogenous protein sharing structural similarities with the natriuretic peptides [NPs; atrial (ANP), B‐type (BNP) and C‐type (CNP) NP], which are hormones known for their crucial role in maintaining pressure/volume homeostasis. Osteocrin competes with the NPs for binding to the receptor involved in their clearance (NPR‐C). In the present study, having identified, for the first time, the major circulating form of OSTN in human and ovine plasma, we examined the integrated haemodynamic, endocrine and renal effects of vehicle‐controlled incremental infusions of ovine proOSTN (83–133) and its metabolism in eight conscious normal sheep. Incremental i.v. doses of OSTN produced stepwise increases in circulating concentrations of the peptide, and its metabolic clearance rate was inversely proportional to the dose. Osteocrin increased plasma levels of ANP, BNP and CNP in a dose‐dependent manner, together with concentrations of their intracellular second messenger, cGMP. Increases in plasma cGMP were associated with progressive reductions in arterial pressure and central venous pressure. Plasma cAMP, renin and aldosterone were unchanged. Despite significant increases in urinary cGMP levels, OSTN administration was not associated with natriuresis or diuresis in normal sheep. These results support OSTN as an endogenous ligand for NPR‐C in regulating plasma concentrations of NPs and associated cGMP‐mediated bioactivity. Collectively, our findings support a role for OSTN in maintaining cardiovascular homeostasis.

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“…In addition to tight junctions, endothelial cells control permeability via cytoskeleton components, such as actin filaments and microtubules, and such mechanisms may also underlie the protective effects of CNP. A good example being GEF-H1, a microtubule-associated RhoA-activating factor, that interacts with NPR-C ( Nishida et al, 2021 ). Upon NPR-C activation, GEF-H1 increases endothelial permeability via enhanced exocytosis and cytoskeletal modulation ( Birukova et al, 2006 ; Pathak and Dermardirossian, 2013 ; Tian et al, 2014 ), perhaps explaining the BBB disruption in gbCNP –/– animals.…”

Section: Discussionmentioning

confidence: 99%

C-type natriuretic peptide preserves central neurological function by maintaining blood-brain barrier integrity

Pérez‐Ternero

Pallier

Tremoleda

et al. 2022

Front. Mol. Neurosci.

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C-type natriuretic peptide (CNP) is highly expressed in the central nervous system (CNS) and key to neuronal development; however, a broader role for CNP in the CNS remains unclear. To address this deficit, we investigated behavioral, sensory and motor abnormalities and blood-brain barrier (BBB) integrity in a unique mouse model with inducible, global deletion of CNP (gbCNP–/–). gbCNP–/– mice and wild-type littermates at 12 (young adult) and 65 (aged) weeks of age were investigated for changes in gait and motor coordination (CatWalk™ and rotarod tests), anxiety-like behavior (open field and elevated zero maze tests), and motor and sensory function (modified neurological severity score [mNSS] and primary SHIRPA screen). Vascular permeability was assessed in vivo (Miles assay) with complementary in vitro studies conducted in primary murine brain endothelial cells. Young adult gbCNP–/– mice had normal gait but reduced motor coordination, increased locomotor activity in the open field and elevated zero maze, and had a higher mNSS score. Aged gbCNP–/– animals developed recurrent spontaneous seizures and had impaired gait and wide-ranging motor and sensory dysfunction. Young adult and aged gbCNP–/– mice exhibited increased BBB permeability, which was partially restored in vitro by CNP administration. Cultured brain endothelial cells from gbCNP–/– mice had an abnormal ZO-1 protein distribution. These data suggest that lack of CNP in the CNS impairs tight junction protein arrangement and increases BBB permeability, which is associated with changes in locomotor activity, motor coordination and late-onset seizures.

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Natriuretic peptide receptor-C releases and activates guanine nucleotide-exchange factor H1 in a ligand-dependent manner

Cited by 4 publications

References 24 publications

The natriuretic peptide receptor agonist osteocrin disperses Pseudomonas aeruginosa biofilm

The natriuretic peptide receptor agonist osteocrin disperses Pseudomonas aeruginosa biofilm

Haemodynamic, hormonal and renal actions of osteocrin in normal sheep

C-type natriuretic peptide preserves central neurological function by maintaining blood-brain barrier integrity

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