Gene Symbol: Npr3
Description: natriuretic peptide receptor 3
Alias: ANP-CR, NPRC, atrial natriuretic peptide receptor 3, ANP-C, ANPR-C, ANPRC, Atrial natriuretic peptide clearence receptor 3, NPR-C, atrial natriuretic peptide C-type receptor, atrial natriuretic peptide clearance receptor, atrial natriuretic peptide receptor type C, natriuretic peptide receptor C/guanylate cyclase C (atrionatriuretic peptide receptor C)
Species: rat
Products:     Npr3

Top Publications

  1. Mouawad R, Li Y, Anand Srivastava M. Atrial natriuretic peptide-C receptor-induced attenuation of adenylyl cyclase signaling activates phosphatidylinositol turnover in A10 vascular smooth muscle cells. Mol Pharmacol. 2004;65:917-24 pubmed
  2. Hobbs A, Foster P, Prescott C, Scotland R, Ahluwalia A. Natriuretic peptide receptor-C regulates coronary blood flow and prevents myocardial ischemia/reperfusion injury: novel cardioprotective role for endothelium-derived C-type natriuretic peptide. Circulation. 2004;110:1231-5 pubmed
    ..Moreover, this newly defined pathway represents a protective mechanism against I/R injury and a novel target for therapeutic intervention in ischemic cardiovascular disorders. ..
  3. Anand Srivastava M, Sehl P, Lowe D. Cytoplasmic domain of natriuretic peptide receptor-C inhibits adenylyl cyclase. Involvement of a pertussis toxin-sensitive G protein. J Biol Chem. 1996;271:19324-9 pubmed
    ..Our results provide evidence that the 37-amino acid cytoplasmic domain of NPR-C is sufficient for signaling inhibition of adenylyl cyclase through a pertussis toxin-sensitive G protein. ..
  4. Bennett B, Bennett G, Vitangcol R, Jewett J, Burnier J, Henzel W, et al. Extracellular domain-IgG fusion proteins for three human natriuretic peptide receptors. Hormone pharmacology and application to solid phase screening of synthetic peptide antisera. J Biol Chem. 1991;266:23060-7 pubmed
  5. Sabbatini M, Rodríguez M, Di Carlo M, Davio C, Vatta M, Bianciotti L. C-type natriuretic peptide enhances amylase release through NPR-C receptors in the exocrine pancreas. Am J Physiol Gastrointest Liver Physiol. 2007;293:G987-94 pubmed
    ..The augmentation in cGMP supports activation of NPR-A/NPR-B receptors probably involved in calcium influx. Present findings give evidence that CNP is a potential direct regulator of pancreatic function. ..
  6. El Andalousi J, Li Y, Anand Srivastava M. Natriuretic peptide receptor-C agonist attenuates the expression of cell cycle proteins and proliferation of vascular smooth muscle cells from spontaneously hypertensive rats: role of Gi proteins and MAPkinase/PI3kinase signaling. PLoS ONE. 2013;8:e76183 pubmed publisher
    ..It may be suggested that C-ANP4-23 could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension, atherosclerosis and restenosis. ..
  7. Del Ry S, Cabiati M, Vozzi F, Battolla B, Caselli C, Forini F, et al. Expression of C-type natriuretic peptide and its receptor NPR-B in cardiomyocytes. Peptides. 2011;32:1713-8 pubmed publisher
    ..By immunostaining of tissue sections, CNP was detected in both endothelium and cardiomyocytes. Expression of CNP in cardiac cells at gene and protein levels suggests that the heart is actively involved in the production of CNP. ..
  8. Pereira V, Costa A, Rosa E Silva A, Vieira M, Reis A. Regulation of steroidogenesis by atrial natriuretic peptide (ANP) in the rat testis: differential involvement of GC-A and C receptors. Peptides. 2008;29:2024-32 pubmed publisher
    ..To this extent, our results suggest the existence of a local and complex peptidergic system in the rat testis, involving ANP and its receptors that could importantly modulate the androgen biosynthesis. ..
  9. Li Y, Madiraju P, Anand Srivastava M. Knockdown of natriuretic peptide receptor-A enhances receptor C expression and signalling in vascular smooth muscle cells. Cardiovasc Res. 2012;93:350-9 pubmed publisher
    ..These results demonstrate that knockdown of NPR-A up-regulates the expression of NPR-C, Gi? proteins, and NPR-C-linked AC signalling and suggests a cross-talk between NPR-A and NPR-C. ..

Scientific Experts

More Information


  1. Zhou H, Murthy K. Identification of the G protein-activating sequence of the single-transmembrane natriuretic peptide receptor C (NPR-C). Am J Physiol Cell Physiol. 2003;284:C1255-61 pubmed
    ..We conclude that the 17-amino acid sequence (R(469) to R(485)) in the middle region of the intracellular domain of NPR-C is both necessary and sufficient for activation of G proteins and effector enzymes. ..
  2. Moffatt P, Thomas G, Sellin K, Bessette M, Lafrenière F, Akhouayri O, et al. Osteocrin is a specific ligand of the natriuretic Peptide clearance receptor that modulates bone growth. J Biol Chem. 2007;282:36454-62 pubmed
  3. Oliver P, Fox J, Kim R, Rockman H, Kim H, Reddick R, et al. Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A. Proc Natl Acad Sci U S A. 1997;94:14730-5 pubmed
    ..Thus complete absence of NPRA causes hypertension in mice and leads to cardiac hypertrophy and, particularly in males, lethal vascular events similar to those seen in untreated human hypertensive patients. ..
  4. He X, Dukkipati A, Garcia K. Structural determinants of natriuretic peptide receptor specificity and degeneracy. J Mol Biol. 2006;361:698-714 pubmed
  5. Hu P, Zhao X, Wang J, Kong H, Hu B, Lu L, et al. Paradoxical expressions of natriuretic peptide receptor-C and neutral endopeptidase account for C-type natriuretic peptide decline during the progression of experimental obstructive nephropathy. J Renin Angiotensin Aldosterone Syst. 2014;15:458-65 pubmed publisher
    ..A high level of CNP may contribute to the elevated expression of NPR-B in the early phase of UUO. More interestingly, paradoxical expressions of NPR-C and NEP may account for the decline of CNP in the obstructed kidneys. ..
  6. Jaubert J, Jaubert F, Martin N, Washburn L, Lee B, Eicher E, et al. Three new allelic mouse mutations that cause skeletal overgrowth involve the natriuretic peptide receptor C gene (Npr3). Proc Natl Acad Sci U S A. 1999;96:10278-83 pubmed
    ..The Npr3 gene coding for type C receptor for natriuretic peptides (NPR-C), which is mainly involved in the clearance of the ..
  7. Nader L, Lahoud L, Chouery E, Aftimos G, Bois P, Farès N. B-type natriuretic peptide receptors in hypertrophied adult rat cardiomyocytes. Ann Cardiol Angeiol (Paris). 2010;59:20-4 pubmed publisher
    ..This relationship may amplify beneficial paracrine/autocrine effects of BNP on cardiac remodelling in response to hemodynamic overload. ..
  8. Matsukawa N, Grzesik W, Takahashi N, Pandey K, Pang S, Yamauchi M, et al. The natriuretic peptide clearance receptor locally modulates the physiological effects of the natriuretic peptide system. Proc Natl Acad Sci U S A. 1999;96:7403-8 pubmed
    ..To test how NPRC affects the cardiovascular and renal systems, we inactivated its gene (Npr3) in mice by homologous recombination...
  9. Sabbatini M, Vatta M, Vescina C, Gonzales S, Fernandez B, Bianciotti L. NPR-C receptors are involved in C-type natriuretic peptide response on bile secretion. Regul Pept. 2003;116:13-20 pubmed
    ..The present study shows that CNP modulates bile secretion in the rat, suggesting that CNP may be part of the large family of peptides involved in the regulation of gastrointestinal physiology. ..
  10. Trachte G. Neuronal regulation and function of natriuretic peptide receptor C. Peptides. 2005;26:1060-7 pubmed
    ..These studies have identified an inhibitory influence of NPR-C on adrenergic neurotransmission by a calcium-dependent process. ..
  11. Sabbatini M, Villagra A, Davio C, Vatta M, Fernandez B, Bianciotti L. Atrial natriuretic factor stimulates exocrine pancreatic secretion in the rat through NPR-C receptors. Am J Physiol Gastrointest Liver Physiol. 2003;285:G929-37 pubmed
    ..Furthermore, CCK and secretin appear not to be involved in ANF response. Present findings support that ANF exerts a stimulatory effect on pancreatic exocrine secretion mediated by NPR-C receptors coupled to the phosphoinositide pathway. ..
  12. Saha S, Li Y, Lappas G, Anand Srivastava M. Activation of natriuretic peptide receptor-C attenuates the enhanced oxidative stress in vascular smooth muscle cells from spontaneously hypertensive rats: implication of Gialpha protein. J Mol Cell Cardiol. 2008;44:336-44 pubmed
    ..These results suggest that C-ANP(4-23) decreases the enhanced oxidative stress in SHR by attenuating the enhanced expression of Gialpha proteins and also the enhanced levels of NADPH oxidase. ..
  13. Engel A, Schoenfeld J, Lowe D. A single residue determines the distinct pharmacology of rat and human natriuretic peptide receptor-C. J Biol Chem. 1994;269:17005-8 pubmed
    ..To our knowledge, this is the first example of a single transmembrane domain receptor for which a single residue dictates the ligand binding properties; previous examples are limited to seven transmembrane receptors. ..
  14. Alli A, Gower W. Molecular approaches to examine the phosphorylation state of the C type natriuretic peptide receptor. J Cell Biochem. 2010;110:985-94 pubmed publisher
    The intracellular domain of the C type natriuretic peptide receptor (NPRC) contains one threonine and several serine residues where phosphorylation is thought to occur...
  15. Lin X, Hanze J, Heese F, Sodmann R, Lang R. Gene expression of natriuretic peptide receptors in myocardial cells. Circ Res. 1995;77:750-8 pubmed
    ..The mRNAs for all three NPRs were also found in cultures of fibroblasts from the rat heart. In contrast to the myocytes, large increases in cGMP were observed in response not only to ANP but also to CNP. ..
  16. Abdelalim E, Tooyama I. NPR-C is expressed in the cholinergic and dopaminergic amacrine cells in the rat retina. Peptides. 2010;31:180-3 pubmed publisher
    ..These data suggest that natriuretic peptides may play a role in maintaining the retinal functions via interaction with NPR-C. ..
  17. Arejian M, Li Y, Anand Srivastava M. Nitric oxide attenuates the expression of natriuretic peptide receptor C and associated adenylyl cyclase signaling in aortic vascular smooth muscle cells: role of MAPK. Am J Physiol Heart Circ Physiol. 2009;296:H1859-67 pubmed publisher
  18. Thompson I, Chand A, Jonas K, Burrin J, Steinhelper M, Wheeler Jones C, et al. Molecular characterisation and functional interrogation of a local natriuretic peptide system in rodent pituitaries, alphaT3-1 and LbetaT2 gonadotroph cells. J Endocrinol. 2009;203:215-29 pubmed publisher
    ..Nppc, along with all three natriuretic peptide receptors (Npr1, Npr2 and Npr3), was expressed in both alphaT3-1 and LbetaT2 cells and primary mouse pituitary tissue, yet the genes for atrial-(..
  19. Khambata R, Panayiotou C, Hobbs A. Natriuretic peptide receptor-3 underpins the disparate regulation of endothelial and vascular smooth muscle cell proliferation by C-type natriuretic peptide. Br J Pharmacol. 2011;164:584-97 pubmed publisher
    ..As GPCRs are well-known to control cell proliferation, we investigated if NPR3 activation underlies effects of CNP on endothelial and vascular smooth muscle cell mitogenesis...
  20. Murthy K, Teng B, Jin J, Makhlouf G. G protein-dependent activation of smooth muscle eNOS via natriuretic peptide clearance receptor. Am J Physiol. 1998;275:C1409-16 pubmed
  21. Pitzalis M, Sarzani R, Dessì Fulgheri P, Iacoviello M, Forleo C, Lucarelli K, et al. Allelic variants of natriuretic peptide receptor genes are associated with family history of hypertension and cardiovascular phenotype. J Hypertens. 2003;21:1491-6 pubmed
    ..associations between a family history of hypertension, cardiovascular phenotype and allelic variants of Npr1 and Npr3, two candidate genes that codify for natriuretic peptide receptors...
  22. Lin D, Chai Y, Izadpanah R, Braun S, Alt E. NPR3 protects cardiomyocytes from apoptosis through inhibition of cytosolic BRCA1 and TNF-α. Cell Cycle. 2016;15:2414-9 pubmed publisher
    Natriuretic peptide receptor 3 (NPR3) is a clearance receptor by binding and internalizing natriuretic peptides (NPs) for ultimate degradation. Patients with cardiac failure show elevated NPs...
  23. Costa M, Elesgaray R, Balaszczuk A, Arranz C. Role of NPR-C natriuretic receptor in nitric oxide system activation induced by atrial natriuretic peptide. Regul Pept. 2006;135:63-8 pubmed
    ..In kidney, aorta and ventricle, NOS activation would also involve NPR-A and/or B. ANP would interact with NPR-C coupled via Gi to activation Ca2+ -dependent NOS. ..
  24. Rollin R, Mediero A, Fernandez Cruz A, Fernández Durango R. Downregulation of the atrial natriuretic peptide/natriuretic peptide receptor-C system in the early stages of diabetic retinopathy in the rat. Mol Vis. 2005;11:216-24 pubmed
    ..One and 3 months after the onset of diabetes, the expression of ANP mRNA and that of its receptors (NPRA, NPRB, NPRC) and the immunoreactive ANP was quantified in retinal tissue by quantitative real time reverse transcription-..
  25. Wong L, Wee A, Lim J, Ng J, Chong J, Liew O, et al. Natriuretic peptide receptor 3 (NPR3) is regulated by microRNA-100. J Mol Cell Cardiol. 2015;82:13-21 pubmed publisher
    Natriuretic peptide receptor 3 (NPR3) is the clearance receptor for the cardiac natriuretic peptides (NPs). By modulating the level of NPs, NPR3 plays an important role in cardiovascular homeostasis...
  26. Ogawa H, Qiu Y, Huang L, Tam Chang S, Young H, Misono K. Structure of the atrial natriuretic peptide receptor extracellular domain in the unbound and hormone-bound states by single-particle electron microscopy. FEBS J. 2009;276:1347-55 pubmed publisher
    ..The results also support the proposed rotation mechanism for transmembrane signaling by the ANP receptor. ..
  27. Trachte G. Natriuretic peptides suppress protein kinase C activity to reduce evoked dopamine efflux from pheochromocytoma (PC12) cells. Endocrinology. 2003;144:94-100 pubmed
    ..These data suggest that C-type natriuretic peptide attenuates neurotransmitter efflux by a mechanism involving suppression of neuronal protein kinase C activity via an interaction with the NPR-C. ..
  28. Xu G, Tian J, Zhong Y, Yang X. Natriuretic peptide receptors are expressed in rat retinal ganglion cells. Brain Res Bull. 2010;82:188-92 pubmed publisher
  29. Boumati M, Li Y, Anand Srivastava M. Modulation of ANP-C receptor signaling by endothelin-1 in A-10 smooth muscle cells. Arch Biochem Biophys. 2002;401:178-86 pubmed
    ..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. ..
  30. Venkatesan B, Tumala A, Subramanian V, Vellaichamy E. Transient silencing of Npr3 gene expression improved the circulatory levels of atrial natriuretic peptides and attenuated ?-adrenoceptor activation- induced cardiac hypertrophic growth in experimental rats. Eur J Pharmacol. 2016;782:44-58 pubmed publisher
    ..Hence, we sought to determine the level of Npr3 gene (coding for NPR-C) expression in the Isoproterenol (ISO) treated Wistar rats...