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Gene Review

Npr2  -  natriuretic peptide receptor 2

Mus musculus

Synonyms: ANP-B, ANPR-B, Atrial natriuretic peptide receptor 2, Atrial natriuretic peptide receptor type B, GC-B, ...
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Disease relevance of Npr2

  • CONCLUSIONS: The results show that diabetes in mice confers increased NPR-B gene expression in the heart, suggesting that increased NPR-B signalling may affect development of diabetic cardiomyopathy [1].
  • Our results may explain one of the molecular mechanisms of the growth stimulating action of CNP and suggest that activation of the CNP/GC-B pathway may be effective as a novel therapeutic strategy for achondroplasia [2].
  • In humans, homozygous NPR-B mutations are the cause of acromesomelic dysplasia, Maroteaux type (AMDM), a severe form of disproportionate dwarfism [3].
  • They suggest that the effects of S1P on vascular disease and wound healing may be mediated in part through inhibition of NPR-B [4].

High impact information on Npr2


Biological context of Npr2


Anatomical context of Npr2

  • In cultured chondrocytes of cn/cn mice, stimulus with CNP did not significantly increase intracellular cGMP concentration, whereas it increased in +/+ mice [7].
  • A considerable amount of GC-B mRNA was present in fetal mouse tibias [14].
  • Relative expression levels of GC-B1, GC-B2, and GC-B3 vary across tissues and as a function of in vitro culture; the relative amount of GC-B2 to GC-B1 is repressed in cultured smooth muscle cells relative to endogenous ratios in the medial layer cells of the aorta [9].
  • 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 [15].
  • Therefore, some or all of the GC-B receptor appears to exist on the apical membrane of uterine epithelial cells [16].

Associations of Npr2 with chemical compounds

  • Mice with STZ-induced type-I diabetes also showed an increase of heart NPR-B mRNA expression at 12 weeks, but not at 3, 6 or 9 weeks after STZ-treatment [1].
  • 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 [17].
  • We have also demonstrated that GC of NPR-B is sensitive to methylene blue [18].
  • The effects of the mitogens on cellular cyclic GMP are fully explained by a direct and stable inactivation of GC-B [19].
  • The activity of natriuretic peptide receptor-B (NPR-B) was unchanged after the addition of retinoid to the culture system [20].

Physical interactions of Npr2

  • GC-B2 binds CNP, but the ligand fails to activate the cyclase, while GC-B3 fails to bind ligand [9].

Regulatory relationships of Npr2

  • The NPR-A is selectively expressed by LLC-PK1 epithelial cells and the NPR-B by NIH-3T3 fibroblast cells [18].
  • We conclude that CNP is synthesized in the pituitary, where it is located predominantly in gonadotropes, and GC-B receptors expressed in the pituitary mediate the direct effects of CNP in gonadotropes [21].

Other interactions of Npr2


Analytical, diagnostic and therapeutic context of Npr2


  1. Heart specific up-regulation of genes for B-type and C-type natriuretic peptide receptors in diabetic mice. Christoffersen, C., Bartels, E.D., Nielsen, L.B. Eur. J. Clin. Invest. (2006) [Pubmed]
  2. Complementary antagonistic actions between C-type natriuretic peptide and the MAPK pathway through FGFR-3 in ATDC5 cells. Ozasa, A., Komatsu, Y., Yasoda, A., Miura, M., Sakuma, Y., Nakatsuru, Y., Arai, H., Itoh, N., Nakao, K. Bone (2005) [Pubmed]
  3. C-type natriuretic peptide in growth: a new paradigm. Olney, R.C. Growth Horm. IGF Res. (2006) [Pubmed]
  4. Sphingosine-1-phosphate inhibits C-type natriuretic peptide activation of guanylyl cyclase B (GC-B/NPR-B). Abbey-Hosch, S.E., Cody, A.N., Potter, L.R. Hypertension (2004) [Pubmed]
  5. Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway. Yasoda, A., Komatsu, Y., Chusho, H., Miyazawa, T., Ozasa, A., Miura, M., Kurihara, T., Rogi, T., Tanaka, S., Suda, M., Tamura, N., Ogawa, Y., Nakao, K. Nat. Med. (2004) [Pubmed]
  6. 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]
  7. A loss-of-function mutation in natriuretic peptide receptor 2 (Npr2) gene is responsible for disproportionate dwarfism in cn/cn mouse. Tsuji, T., Kunieda, T. J. Biol. Chem. (2005) [Pubmed]
  8. Calcium-dependent dephosphorylation mediates the hyperosmotic and lysophosphatidic acid-dependent inhibition of natriuretic peptide receptor-B/guanylyl cyclase-B. Potthast, R., Abbey-Hosch, S.E., Antos, L.K., Marchant, J.S., Kuhn, M., Potter, L.R. J. Biol. Chem. (2004) [Pubmed]
  9. Regulation of the guanylyl cyclase-B receptor by alternative splicing. Tamura, N., Garbers, D.L. J. Biol. Chem. (2003) [Pubmed]
  10. Genetic mapping of the C-type natriuretic peptide receptor (Npr2) gene to mouse chromosome 4. Nuglozeh, E., Kozak, L.P. Mamm. Genome (1997) [Pubmed]
  11. Altered expression of natriuretic peptide receptors in proANP gene disrupted mice. Vera, N., Tse, M.Y., Watson, J.D., Sarda, S., Steinhelper, M.E., John, S.W., Flynn, T.G., Pang, S.C. Cardiovasc. Res. (2000) [Pubmed]
  12. Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide. Suda, M., Ogawa, Y., Tanaka, K., Tamura, N., Yasoda, A., Takigawa, T., Uehira, M., Nishimoto, H., Itoh, H., Saito, Y., Shiota, K., Nakao, K. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  13. C-type natriuretic peptide in reproduction, pregnancy and fetal development. Walther, T., Stepan, H. J. Endocrinol. (2004) [Pubmed]
  14. Natriuretic peptide regulation of endochondral ossification. Evidence for possible roles of the C-type natriuretic peptide/guanylyl cyclase-B pathway. Yasoda, A., Ogawa, Y., Suda, M., Tamura, N., Mori, K., Sakuma, Y., Chusho, H., Shiota, K., Tanaka, K., Nakao, K. J. Biol. Chem. (1998) [Pubmed]
  15. 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]
  16. Seminal plasma factors that cause large elevations in cellular cyclic GMP are C-type natriuretic peptides. Chrisman, T.D., Schulz, S., Potter, L.R., Garbers, D.L. J. Biol. Chem. (1993) [Pubmed]
  17. 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]
  18. Different ATP effects on natriuretic peptide receptor subtypes in LLC-PK1 and NIH-3T3 cells. Shigematsu, Y., Vaughn, J., Touchard, C.L., Frohlich, E.D., Alam, J., Cole, F.E. Life Sci. (1993) [Pubmed]
  19. Reciprocal antagonism coordinates C-type natriuretic peptide and mitogen-signaling pathways in fibroblasts. Chrisman, T.D., Garbers, D.L. J. Biol. Chem. (1999) [Pubmed]
  20. 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]
  21. C-type natriuretic peptide (CNP) in the pituitary: is CNP an autocrine regulator of gonadotropes? McArdle, C.A., Olcese, J., Schmidt, C., Poch, A., Kratzmeier, M., Middendorff, R. Endocrinology (1994) [Pubmed]
  22. Effects of different natriuretic peptides on nitric oxide synthesis in macrophages. Kiemer, A.K., Vollmar, A.M. Endocrinology (1997) [Pubmed]
  23. Critical roles of the guanylyl cyclase B receptor in endochondral ossification and development of female reproductive organs. Tamura, N., Doolittle, L.K., Hammer, R.E., Shelton, J.M., Richardson, J.A., Garbers, D.L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  24. C-type natriuretic peptide (CNP) effects in anterior pituitary cell lines: evidence for homologous desensitisation of CNP-stimulated cGMP accumulation in alpha T3-1 gonadotroph-derived cells. Fowkes, R.C., Forrest-Owen, W., McArdle, C.A. J. Endocrinol. (2000) [Pubmed]
  25. New aspects of Leydig cell function. Middendorff, R., Müller, D., Paust, H.J., Holstein, A.F., Davidoff, M.S. Adv. Exp. Med. Biol. (1997) [Pubmed]
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