Disease relevance of Npr3

• From these studies it may be suggested that the downregulation of ANP-C receptors by increased levels of endothelin in vivo may be one of the possible mechanisms for the pathophysiology of hypertension [1].
• Further studies should address the possible involvement of the ANP/NPRC system in the pathophysiology of diabetic retinopathy [2].
• In adrenals, unlike controls, FR50 rats enhanced ANP-B receptor density whereas they decreased both ANP-C receptor density and expression after 72 h dehydration [3].
• Densities (Bmax) and dissociation constants (Kd) of both the biologically active (ANPA) and clearance receptors (ANPC) were evaluated in glomerular and papillary membranes from A-V fistula rats (n = 18) and sham-operated controls (n = 20) [4].
• However, stimulating NPR-C receptor with des-(Gln(18), Ser(19),Gly(20),Leu(21),Gly(22))-ANP fragment 4-23 amide (C-ANP) also increased hepatocyte tolerance to hypoxia [5].

Psychiatry related information on Npr3

• Water deprivation increased the B(max) of glomerular binding sites for ANP(1-28) and C-type natriuretic peptide (CNP)(1-22) without modifying their affinity, an effect that was prevented in the presence of C-atrial natriuretic factor (C-ANF), suggesting that natriuretic peptide receptor-C (NPR-C) binding sites might be enhanced [6].

High impact information on Npr3

• The heart expresses the three natriuretic peptide receptors (NPR), namely NPR-A, NPR-B, and NPR-C [7].
• In contrast, C-ANP, which binds only to the ANP C-receptor, had no effects [8].
• These data demonstrate that acetylcholine-evoked release of endothelial CNP activates NPR-C on vascular smooth muscle that via a G(i) coupling promotes Ba(2+)ouabain-sensitive hyperpolarization [9].
• Analysis by RT-PCR revealed the presence of transcripts for NPR-A as well as NPR-B and NPR-C [10].
• We have recently demonstrated that a 37-amino acid peptide corresponding to the cytoplasmic domain of the natriuretic peptide receptor C (NPR-C) inhibited adenylyl cyclase activity via pertussis toxin (PT)-sensitive G(i) protein [11].

Chemical compound and disease context of Npr3

• The mRNA expression of NPR-A and NPR-C was increased, whereas that of ACE and AT1 receptors was decreased in DOCA-salt hypertension [12].

Biological context of Npr3

• These results indicate that C-ANP(4-23) treatment of A10 cells desensitizes ANP-C receptor-mediated inhibition of adenylyl cyclase which may be due to the downregulation of ANP-C receptor and decreased expression of Gialpha proteins to which these receptors are coupled [13].
• However, controversies exist regarding the involvement of ANP-C receptor and adenylyl cyclase/cAMP signal-transduction systems to which these receptors are coupled in mediating these responses [14].
• In addition, AngII treatment stimulated the phosphorylation of Gialpha2 but not of Gialpha3 or ANP-C receptor, as revealed by immunoprecipitation of the proteins using specific antibodies after prelabelling the cells with [32P]orthophosphate [15].
• Similarly, ANP-C receptor gene expression was unaffected in kidneys whereas it was significantly enhanced in adrenals [3].
• When the intracellular signaling coupled to NPR-C receptors was investigated in isolated pancreatic acini, results showed that ANF did not modify basal or forskolin-evoked cAMP formation, but it dose-dependently enhanced phosphoinositide hydrolysis, which was blocked by the selective PLC inhibitor U-73122 [16].

Anatomical context of Npr3

• C-ANP(4-23) [des(Gln(18),Ser(19), Glu(20),Leu(21),Gly(22))ANP(4-23)-NH(2)], a ring-deleted peptide of ANP that interacts specifically with ANP-C receptor, stimulated inositol 1,4,5-tris-phosphate (IP(3)) production (PLC activity) in A10 vascular smooth muscle cells in a concentration- and time-dependent manner [17].
• In the present studies, we have examined the regulation of ANP-C receptor-adenylyl cyclase signal transduction by ANP and [des(Gln(18),Ser(19),Gln(20),Leu(21), Gly(22))ANP(4-23)-NH(2)](C-ANP(4-23)) that interacts specifically with ANP-C receptor in A10 smooth muscle cells (SMC) [13].
• These data indicate that PKC modulates both guanylyl cyclase-coupled and ANP-C natriuretic peptide receptors in cultured astroglia [18].
• Both C-ANP-(4-23), a selective ligand of NPRC, and caffeine had no effect on the acrosome reaction [19].
• In situ hybridization indicated that the salt-induced NPR-C change was attributed mainly to suppressed expression of NPR-C in the podocytes [20].

Associations of Npr3 with chemical compounds

• Atrial natriuretic peptide (ANP) receptors A and B are guanylyl cyclase receptors, whereas ANP-C receptors are coupled to adenylyl cyclase through inhibitory guanine nucleotide (Gi) protein [13].
• An 18-mer antisense phosphorothioate oligodeoxynucleotide (OH-2) targeted at the initiation codon of the ANP-C receptor was used to examine its effects on the expression of the ANP-C receptor and ANP-C-receptor-mediated inhibition of adenylyl cyclase in vascular smooth-muscle cells (A10) [14].
• Angiotensin II modulates ANP-R2/ANP-C receptor-mediated inhibition of adenylyl cyclase in vascular smooth muscle cells: role of protein kinase C [15].
• The main effects were a significant rise in circulating levels of VP and aldosterone, and changes in density of adrenal ANP-binding sites and ANP-C receptor gene expression in both adrenals and kidneys [3].
• Present findings support that ANF exerts a stimulatory effect on pancreatic exocrine secretion mediated by NPR-C receptors coupled to the phosphoinositide pathway [16].

Regulatory relationships of Npr3

• These results suggest that ET-1-induced downregulation of ANP-C receptor and not the overexpression of Gi proteins may be responsible for the attenuation of C-ANP(4-23)-mediated inhibition of adenylyl cyclase activity [1].

Other interactions of Npr3

• Inhibition of atrial natriuretic peptide (ANP) C receptor expression by antisense oligodeoxynucleotides in A10 vascular smooth-muscle cells is associated with attenuation of ANP-C-receptor-mediated inhibition of adenylyl cyclase [14].
• Modulation of ANP-C receptor signaling by endothelin-1 in A-10 smooth muscle cells [1].
• ANP (10(-9) and 3.10(-9)), which binds to NPR-A and NPR-C, dilated preglomerular vessels and constricted efferent arterioles similarly to that found in previous studies [21].
• Modulation of ANP-C receptor signaling by arginine-vasopressin in A-10 vascular smooth muscle cells: role of protein kinase C [22].
• These results suggest a role for the NPR-C in modulation of natriuretic peptide availability and/or adenylate cyclase activity in a subset of central natriuretic peptide circuits concerned with cortical, olfactory and neuroendocrine functions [23].

Analytical, diagnostic and therapeutic context of Npr3

• In addition, treatment of the cells with antisense oligonucleotide and not with sense or missense oligomers resulted in the inhibition of the levels of ANP-C-receptor protein and mRNA as determined by immunoblotting and Northern blotting using antisera against the ANP-C receptor and a cDNA probe of the ANP-C receptor respectively [14].
• Pretreatment of A-10 SMC with ET-1 for 24 h attenuated the expression of ANP-C receptor by about 60% as determined by immunoblotting which was reflected in attenuation of ANP-C-receptor-mediated inhibition of adenylyl cyclase [1].
• These findings suggest that changes in pulmonary ANP and NPR-C expression may contribute to the development of PPE in the remaining lung in the acute phase following pneumonectomy [24].
• The level of NPR-C mRNA expression in the pneumonectomy group was significantly higher than in the control group (4.17 versus 2.19 relative NPR-C mRNA expression, P<0.01) [24].
• PCR and molecular cloning indicated that the intracellular domain of A. australis NPR-C has the same amino acid sequence as Anguilla japonica [25].

References