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Gene Review

Npr3  -  natriuretic peptide receptor 3

Rattus norvegicus

Synonyms: ANP-C, ANP-CR, ANPR-C, Atrial natriuretic peptide clearance receptor, Atrial natriuretic peptide receptor 3, ...
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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


Biological context of Npr3


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


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


Analytical, diagnostic and therapeutic context of Npr3


  1. Modulation of ANP-C receptor signaling by endothelin-1 in A-10 smooth muscle cells. Boumati, M., Li, Y., Anand-Srivastava, M.B. Arch. Biochem. Biophys. (2002) [Pubmed]
  2. Downregulation of the atrial natriuretic peptide/natriuretic peptide receptor-C system in the early stages of diabetic retinopathy in the rat. Rollín, R., Mediero, A., Fernández-Cruz, A., Fernández-Durango, R. Mol. Vis. (2005) [Pubmed]
  3. Effects of dehydration on endocrine regulation of the electrolyte and fluid balance and atrial natriuretic peptide-binding sites in perinatally malnourished adult male rats. Sebaai, N., Lesage, J., Alaoui, A., Dupouy, J.P., Deloof, S. Eur. J. Endocrinol. (2002) [Pubmed]
  4. Regulation of renal glomerular and papillary ANP receptors in rats with experimental heart failure. Yechieli, H., Kahana, L., Haramati, A., Hoffman, A., Winaver, J. Am. J. Physiol. (1993) [Pubmed]
  5. Mechanisms of hepatocyte protection against hypoxic injury by atrial natriuretic peptide. Carini, R., De Cesaris, M.G., Splendore, R., Domenicotti, C., Nitti, M.P., Pronzato, M.A., Albano, E. Hepatology (2003) [Pubmed]
  6. Water deprivation enhances the inhibitory effect of natriuretic peptides on cAMP synthesis in rat renal glomeruli. Woodard, G.E., Li, X., Rosado, J.A. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  7. Differential regulation of natriuretic peptide receptor messenger RNAs during the development of cardiac hypertrophy in the rat. Brown, L.A., Nunez, D.J., Wilkins, M.R. J. Clin. Invest. (1993) [Pubmed]
  8. Prolonged antagonism of alpha 1-adrenergic vasoconstriction in the rat liver by atrial natriuretic peptide. Bilzer, M., Paumgartner, G., Gerbes, A.L. Gastroenterology (1995) [Pubmed]
  9. Release of C-type natriuretic peptide accounts for the biological activity of endothelium-derived hyperpolarizing factor. Chauhan, S.D., Nilsson, H., Ahluwalia, A., Hobbs, A.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  10. Gene expression of natriuretic peptide receptors in myocardial cells. Lin, X., Hänze, J., Heese, F., Sodmann, R., Lang, R.E. Circ. Res. (1995) [Pubmed]
  11. Cytoplasmic domain of natriuretic peptide receptor C constitutes Gi activator sequences that inhibit adenylyl cyclase activity. Pagano, M., Anand-Srivastava, M.B. J. Biol. Chem. (2001) [Pubmed]
  12. Altered expression of vascular natriuretic peptide receptors in experimental hypertensive rats. Lee, J., Kim, S., Jung, M., Oh, Y., Kim, S.W. Clin. Exp. Pharmacol. Physiol. (2002) [Pubmed]
  13. Downregulation of atrial natriuretic peptide ANP-C receptor is associated with alterations in G-protein expression in A10 smooth muscle cells. Anand-Srivastava, M.B. Biochemistry (2000) [Pubmed]
  14. 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. Palaparti, A., Li, Y., Anand-Srivastava, M.B. Biochem. J. (2000) [Pubmed]
  15. Angiotensin II modulates ANP-R2/ANP-C receptor-mediated inhibition of adenylyl cyclase in vascular smooth muscle cells: role of protein kinase C. Palaparti, A., Anand-Srivastava, M.B. J. Mol. Cell. Cardiol. (1998) [Pubmed]
  16. Atrial natriuretic factor stimulates exocrine pancreatic secretion in the rat through NPR-C receptors. Sabbatini, M.E., Villagra, A., Davio, C.A., Vatta, M.S., Fernandez, B.E., Bianciotti, L.G. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  17. Atrial natriuretic peptide-C receptor-induced attenuation of adenylyl cyclase signaling activates phosphatidylinositol turnover in A10 vascular smooth muscle cells. Mouawad, R., Li, Y., Anand-Srivastava, M.B. Mol. Pharmacol. (2004) [Pubmed]
  18. Protein kinase C modulates natriuretic peptide receptors in astroglial cultures from rat brain. Paulding, W.R., Sumners, C. Am. J. Physiol. (1996) [Pubmed]
  19. 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]
  20. Role of natriuretic peptide receptor type C in Dahl salt-sensitive hypertensive rats. Nagase, M., Ando, K., Katafuchi, T., Kato, A., Hirose, S., Fujita, T. Hypertension (1997) [Pubmed]
  21. Natriuretic peptide receptors mediate different responses in rat renal microvessels. Endlich, K., Steinhausen, M. Kidney Int. (1997) [Pubmed]
  22. Modulation of ANP-C receptor signaling by arginine-vasopressin in A-10 vascular smooth muscle cells: role of protein kinase C. Boumati, M., Li, Y., Anand-Srivastava, M.B. Arch. Biochem. Biophys. (2003) [Pubmed]
  23. Expression and glucocorticoid regulation of natriuretic peptide clearance receptor (NPR-C) mRNA in rat brain and choroid plexus. Herman, J.P., Dolgas, C.M., Marcinek, R., Langub, M.C. J. Chem. Neuroanat. (1996) [Pubmed]
  24. Changes in atrial natriuretic peptide concentration and expression of its receptors after pneumonectomy in the rat. Tamura, K., Takamori, S., Mifune, H., Hayashi, A., Shirouzu, K. Clin. Sci. (2000) [Pubmed]
  25. Natriuretic peptides inhibit adenylyl cyclase activity in dispersed eel gill cells. Callahan, W., Nankervis, S., Toop, T. J. Comp. Physiol. B, Biochem. Syst. Environ. Physiol. (2004) [Pubmed]
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