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Npr3  -  natriuretic peptide receptor 3

Mus musculus

Synonyms: ANP-C, ANPR-C, Atrial natriuretic peptide clearance receptor, Atrial natriuretic peptide receptor 3, Atrial natriuretic peptide receptor type C, ...
 
 
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Disease relevance of Npr3

  • NPR-C mRNA levels were greatly reduced in the kidney, lung, and brain by hypoxia in all three genotypes [1].
  • RESULTS: The radiochemical purity of the labeled phage exceeded 95% by strip chromatography using instant thin-layer chromatography/acetone and paper/saline [2].
  • The data presented indicate that one of the primary actions of Pseudomonas aeruginosa exotoxin during experimental infection is the inactivation of elongation factor 2 (EF-2) in various mouse organs [3].
  • Other changes include atrial enlargement and fibrosis, and diffuse myocytolysis, Physiological analyses using ventricular muscle strip preparations from these mice reveal that both myocardial contraction and relaxation parameters are severely impaired [4].
  • HPV sequences from oncogenic types were identified in 52 of 56 (92.9%) by PCR/reverse blot strip assay, and in one additional case using an HPV 16 multiplex PCR assay [5].
 

High impact information on Npr3

  • In permeabilized cells we found that, in agreement with the injection studies, rhodamine-actin incorporated predominantly in a narrow strip of less than 1-microns wide, located at the tip of lamellipodia [6].
  • Nevertheless, differential centrifugation experiments indicated that the two antigens may be recovered in distinct subcellular fractions: this may be related to the unexpected observation that rather low salt concentrations strip the antigens from microsomal fraction [7].
  • The phenotype is consistent with the bone function of NPRC being to clear locally synthesized CNP and modulate its effects [8].
  • Unexpectedly, Npr3 -/- homozygotes have skeletal deformities associated with a considerable increase in bone turnover [8].
  • This phenotype was found to be caused by a recessive mutation, designated longjohn (lgj), that mapped to the proximal region of chromosome 15 [9].
 

Biological context of Npr3

  • Gene expression for NPR-C, which recognizes all natriuretic peptides, was present in the roof plate of the hindbrain and spinal cord and in bilateral stripes just dorsolateral to the floor plate at E12 [10].
  • NPR-C mRNA levels were selectively and significantly reduced (>60%) in kidney, but not in lung, brain, LV, or RV, by dietary salt supplementation in both genotypes [11].
  • We have previously demonstrated organ-selective potentiation of ANP in the pulmonary circulation of hypoxia-adapted animals by local downregulation of its clearance receptor (NPR-C; Li H, Oparil S, Meng QC, Elton T, and Chen Y-F. Am J Physiol Lung Cell Mol Physiol 268: L328-L335, 1995) [11].
  • The selective natriuretic peptide type C receptor (NPR-C) agonist cANF (10(-7) M) significantly decreased heart rate in the presence of isoproterenol (5 x 10(-9) M), as indicated by an increase in the R-R interval of ECGs obtained from Langendorff-perfused hearts [12].
  • The patterns of expression of mRNAs for NPR-B and NPR-C, namely, subtype switching during differentiation from proliferating chondrocytes to hypertrophic chondrocytes, suggest that these receptors might be involved in the growth and differentiation of the growth plate during fetal development in the mouse [13].
 

Anatomical context of Npr3

  • 5. In the PNS, NPR-B and NPR-C transcripts were highly expressed in dorsal root sensory (DRG) and cranial ganglia beginning at E10.5, with NPR-C signal also prominent in adjoining nerves, consistent with Schwann cell localization [10].
  • Competitive inhibition studies showed that 4-23 C-ANP, which is specific of clearance receptors (NPR-C), displaced 90% of the maximum fraction bound, suggesting the predominance of NPR-C in both cell lines [14].
  • CONCLUSIONS: These studies demonstrate that the constitutive overexpression of NPR-C in D-NOD mesangial cells is associated with a decreased response of cGMP to ANP or CNP treatment [14].
  • In these experiments, a "Gi-activator peptide," which consists of a 17-amino acid segment of NPR-C containing a specific Gi protein-activator sequence, was dialyzed into SA node myocytes [12].
  • Effects of C-type natriuretic peptide on ionic currents in mouse sinoatrial node: a role for the NPR-C receptor [12].
 

Associations of Npr3 with chemical compounds

  • This could be due to the lesser availability of the peptides for binding to NPR-A or NPR-B or to an inhibitory effect on NP-dependent guanylate cyclase activity via the activation of NPR-C [14].
  • Both C-ANP-(4-23), a selective ligand of NPRC, and caffeine had no effect on the acrosome reaction [15].
  • Exposure of MC3T3-E1 cells to 1 microM retinoid caused increases in the levels of C-type natriuretic peptide (CNP) and natriuretic peptide receptor-C (NPR-C) [16].
  • On grids soaked in sodium dodecyl sulfate the abnormal tubulofilaments were found in stages of fragmentation, an outer coat appearing t0 strip from the surface to reveal thinner fibrillary structures resembling scrapie-associated fibrils (SAF) [17].
  • An irreversible inhibition of the electrically induced contractions of mouse vas deferens is caused by irradiation (at 254 nm) of the muscle strip in the presence of AZ-DTLET (1 nM) [18].
 

Regulatory relationships of Npr3

  • These results provide the first demonstration that CNP has a negative chronotropic effect on heart rate and suggest that this effect is mediated by selectively activating NPR-C and reducing ICa(L) through coupling to Gi protein [12].
  • The vertebrate Emx genes are expressed in a nested pattern in early embryonic cerebral cortex, such that a medial strip of cortex expresses Emx2 but not Emx1 [19].
 

Other interactions of Npr3

  • Increased expression of NPR-C in D-NOD cells was associated with an increase of ANP internalization rate at 37 degrees C, indicating that these receptors were functional [14].
  • When cultures were denuded of cells in a 1-mm-wide strip, all three cell types migrated into the denuded area [20].
  • Further identification was obtained from RNase protection assay and reverse transcription-polymerase chain reaction, which also demonstrated the higher expression of NPR-C mRNA in D-NOD cells [14].
  • Further support for an NPR-C-mediated inhibition of ICa(L) in SA node myocytes was obtained by altering the functional coupling between the G protein Gi and NPR-C [12].
  • METHODS: Female mice, both control and nNOS knockout, underwent voiding, urodynamic and muscle strip testing as well as histologic studies [21].
 

Analytical, diagnostic and therapeutic context of Npr3

  • Instead of being applied at the surface of the gel in a sample cup, the sample is introduced into the gel during the immobilized pH gradient strip rehydration step [22].
  • Physiologic evaluation consisted of cystometric analyses, and muscle strip studies in response to cholinergic and electrical stimulation [23].
  • Analysis of the cells using a PCR/reverse blot strip assay, which amplifies a portion of the L1 open reading frame, was strongly positive [24].
  • Electrophoresis was run in the presence of 16-BAC, the strip from the gel containing separated proteins was cut out and was re-run on SDS-PAGE [25].
  • A statistically significant correlation was observed on an individual tumor basis between the FI in the first 10 micrometer strip around the charcoal and the pO(2) determined by EPR oximetry (Wilcoxon signed rank test: P<0.001) [26].

References

  1. Hypoxia reduces atrial natriuretic peptide clearance receptor gene expression in ANP knockout mice. Sun, J.Z., Chen, S.J., Li, G., Chen, Y.F. Am. J. Physiol. Lung Cell Mol. Physiol. (2000) [Pubmed]
  2. Investigations of a (99m)Tc-labeled bacteriophage as a potential infection-specific imaging agent. Rusckowski, M., Gupta, S., Liu, G., Dou, S., Hnatowich, D.J. J. Nucl. Med. (2004) [Pubmed]
  3. Mechanism of action of Pseudomonas aeruginosa exotoxin A in experimental mouse infections: adenosine diphosphate ribosylation of elongation factor 2. Pavlovskis, O.R., Iglewski, B.H., Pollack, M. Infect. Immun. (1978) [Pubmed]
  4. Beta-tropomyosin overexpression induces severe cardiac abnormalities. Muthuchamy, M., Boivin, G.P., Grupp, I.L., Wieczorek, D.F. J. Mol. Cell. Cardiol. (1998) [Pubmed]
  5. Detection of specific human papillomavirus types in paraffin-embedded sections of cervical carcinomas. Bryan, J.T., Taddeo, F., Skulsky, D., Jansen, K.U., Frain, B.M., Qadadri, B., Brown, D.R. J. Med. Virol. (2006) [Pubmed]
  6. Control of actin polymerization in live and permeabilized fibroblasts. Symons, M.H., Mitchison, T.J. J. Cell Biol. (1991) [Pubmed]
  7. Characterization of cytoplasmically oriented Golgi proteins with a monoclonal antibody. Chicheportiche, Y., Vassalli, P., Tartakoff, A.M. J. Cell Biol. (1984) [Pubmed]
  8. The natriuretic peptide clearance receptor locally modulates the physiological effects of the natriuretic peptide system. Matsukawa, N., Grzesik, W.J., Takahashi, N., Pandey, K.N., Pang, S., Yamauchi, M., Smithies, O. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. Three new allelic mouse mutations that cause skeletal overgrowth involve the natriuretic peptide receptor C gene (Npr3). Jaubert, J., Jaubert, F., Martin, N., Washburn, L.L., Lee, B.K., Eicher, E.M., Guénet, J.L. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  10. Embryonic expression and multifunctional actions of the natriuretic peptides and receptors in the developing nervous system. DiCicco-Bloom, E., Lelièvre, V., Zhou, X., Rodriguez, W., Tam, J., Waschek, J.A. Dev. Biol. (2004) [Pubmed]
  11. Dietary salt supplementation selectively downregulates NPR-C receptor expression in kidney independently of ANP. Sun, J.Z., Chen, S.J., Majid-Hasan, E., Oparil, S., Chen, Y.F. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  12. Effects of C-type natriuretic peptide on ionic currents in mouse sinoatrial node: a role for the NPR-C receptor. Rose, R.A., Lomax, A.E., Kondo, C.S., Anand-Srivastava, M.B., Giles, W.R. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  13. Concentration of mRNA for the natriuretic peptide receptor-C in hypertrophic chondrocytes of the fetal mouse tibia. Yamashita, Y., Takeshige, K., Inoue, A., Hirose, S., Takamori, A., Hagiwara, H. J. Biochem. (2000) [Pubmed]
  14. Mesangial cells from diabetic NOD mice constitutively express increased density of atrial natriuretic peptide C receptors. Ardaillou, N., Placier, S., Striker, L., Striker, G., Ardaillou, R. Kidney Int. (1999) [Pubmed]
  15. The expression of atrial natriuretic peptide in the oviduct and its functions in pig spermatozoa. Zhang, M., Hong, H., Zhou, B., Jin, S., Wang, C., Fu, M., Wang, S., Xia, G. J. Endocrinol. (2006) [Pubmed]
  16. Stimulation by retinoids of the natriuretic peptide system of osteoblastic MC3T3-E1 cells. Inoue, A., Otsuka, E., Hiruma, Y., Hirose, S., Furuya, M., Tanaka, S., Hagiwara, H. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  17. Tubulofilaments in negatively stained scrapie-infected brains: relationship to scrapie-associated fibrils. Narang, H.K., Asher, D.M., Gajdusek, D.C. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  18. Highly selective photoaffinity labeling of mu and delta opioid receptors. Garbay-Jaureguiberry, C., Robichon, A., Daugé, V., Rossignol, P., Roques, B.P. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  19. Emx2 is required for growth of the hippocampus but not for hippocampal field specification. Tole, S., Goudreau, G., Assimacopoulos, S., Grove, E.A. J. Neurosci. (2000) [Pubmed]
  20. Embryonic fibroblasts that are genetically deficient in low density lipoprotein receptor-related protein demonstrate increased activity of the urokinase receptor system and accelerated migration on vitronectin. Weaver, A.M., Hussaini, I.M., Mazar, A., Henkin, J., Gonias, S.L. J. Biol. Chem. (1997) [Pubmed]
  21. Vesicourethral function in mice with genetic disruption of neuronal nitric oxide synthase. Sutherland, R.S., Kogan, B.A., Piechota, H.J., Bredt, D.S. J. Urol. (1997) [Pubmed]
  22. Sample application by in-gel rehydration improves the resolution of two-dimensional electrophoresis with immobilized pH gradients in the first dimension. Rabilloud, T., Valette, C., Lawrence, J.J. Electrophoresis (1994) [Pubmed]
  23. Altered response to partial bladder outlet obstruction in mice lacking inducible nitric oxide synthase. Lemack, G.E., Zimmern, P.E., Vazquez, D., Connell, J.D., Lin, V.K. J. Urol. (2000) [Pubmed]
  24. Human papillomavirus type 59 immortalized keratinocytes express late viral proteins and infectious virus after calcium stimulation. Lehr, E.E., Qadadri, B., Brown, C.R., Brown, D.R. Virology (2003) [Pubmed]
  25. Mass spectrometrical identification of brain proteins including highly insoluble and transmembrane proteins. Bierczynska-Krzysik, A., Kang, S.U., Silberrring, J., Lubec, G. Neurochem. Int. (2006) [Pubmed]
  26. In vivo colocalization of 2-nitroimidazole EF5 fluorescence intensity and electron paramagnetic resonance oximetry in mouse tumors. Mahy, P., De Bast, M., Gallez, B., Gueulette, J., Koch, C.J., Scalliet, P., Grégoire, V. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. (2003) [Pubmed]
 
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