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Gene Review

Npr1  -  natriuretic peptide receptor 1

Mus musculus

Synonyms: AI893888, ANP-A, ANPR-A, Atrial natriuretic peptide receptor 1, Atrial natriuretic peptide receptor type A, ...
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Disease relevance of Npr1


Psychiatry related information on Npr1


High impact information on Npr1


Chemical compound and disease context of Npr1


Biological context of Npr1

  • These results demonstrate that below normal Npr1 expression leads to a salt-sensitive increase in blood pressure, whereas above normal Npr1 expression lowers blood pressures and protects against high dietary salt [11].
  • Cross-competition experiments with mutated oligonucleotides led to the definition of a consensus sequence (-1372 AaAtRKaNTTCaAcAKTY -1354) for the novel cGMP-RE, which is conserved in the human (75% identity) and mouse (95% identity) Npr1 promoters [12].
  • Our results also suggest roles for Npr1 as well as Apoe in regulation of hypertrophic cell growth [13].
  • Introduction of the GC-A transgene did not alter blood pressure or heart rate as a function of genotype [4].
  • However, introduction of the GC-A transgene reduced cardiac myocyte size in both wild-type and null mice [4].

Anatomical context of Npr1

  • Cardiac myocyte size was larger (approximately 20%) in GC-A null than in wild-type animals [4].
  • Coincident with the reduction in myocyte size, both ANP mRNA and ANP content were significantly reduced by overexpression of GC-A, and this reduction was independent of genotype [4].
  • C-type natriuretic peptide (CNP), in contrast, caused half-maximal relaxation at concentrations of 335 and 146 nM in aortas from either wild-type or null mice, respectively, suggesting that this peptide acted through a receptor other than GC-A [14].
  • Enzyme assays and NPRA-specific Western blots performed on tissues from wild-type mice demonstrate that ANP-activated cGMP synthesis provides a good index of NPRA protein expression, which ranges from maximal in adrenal gland, lung, kidney, and testis to minimal in heart and colon [15].
  • BACKGROUND: Guanylyl cyclase (GC)-A, a natriuretic peptide receptor, lowers blood pressure and inhibits the growth of cardiac myocytes and fibroblasts [16].

Associations of Npr1 with chemical compounds


Physical interactions of Npr1

  • We investigated whether GC-A interacts with AT1A signaling in the heart by target deletion and pharmacological blockade or stimulation of AT1A in mice [16].
  • NF-kappaB binding activity was 4-fold greater in the nuclear extract of Npr1-/- mutant mice hearts as compared with wild-type (Npr1+/+) mice hearts [21].
  • In peripheral organs BNP binds to the natriuretic peptide receptor type A causing increased intracellular cGMP production [22].
  • The constructs having a mutant Ets-1 binding site or lacking this site failed to respond to Ets-1 activation of Npr1 gene transcription [23].

Regulatory relationships of Npr1


Other interactions of Npr1

  • The biological actions of natriuretic peptides are thought to be mediated through the activation of two guanylyl cyclase (GC)-coupled receptor subtypes (GC-A and GC-B) [17].
  • Evidence for a novel natriuretic peptide receptor that prefers brain natriuretic peptide over atrial natriuretic peptide [15].
  • METHODS AND RESULTS: We generated double-knockout (KO) mice for GC-A and AT1A by crossing GC-A-KO mice and AT1A-KO mice and blocked AT1 with a selective antagonist, CS-866 [16].
  • The family of rGCs is rapidly expanding, and it is plausible that there might be additional, as yet undiscovered, rGCs whose function is to provide alternative signalling pathways for one or both of these peptides, particularly given the low affinity of NPRA for BNP [15].
  • Increased effects of C-type natriuretic peptide on cardiac ventricular contractility and relaxation in guanylyl cyclase A-deficient mice [18].

Analytical, diagnostic and therapeutic context of Npr1


  1. Involvement of the NF-kappa B/matrix metalloproteinase pathway in cardiac fibrosis of mice lacking guanylyl cyclase/natriuretic peptide receptor A. Vellaichamy, E., Khurana, M.L., Fink, J., Pandey, K.N. J. Biol. Chem. (2005) [Pubmed]
  2. Ventricular expression of natriuretic peptides in Npr1(-/-) mice with cardiac hypertrophy and fibrosis. Ellmers, L.J., Knowles, J.W., Kim, H.S., Smithies, O., Maeda, N., Cameron, V.A. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  3. Targeted disruption of the gene for natriuretic peptide receptor-A worsens hypoxia-induced cardiac hypertrophy. Klinger, J.R., Warburton, R.R., Pietras, L., Oliver, P., Fox, J., Smithies, O., Hill, N.S. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  4. A genetic model provides evidence that the receptor for atrial natriuretic peptide (guanylyl cyclase-A) inhibits cardiac ventricular myocyte hypertrophy. Kishimoto, I., Rossi, K., Garbers, D.L. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  5. Vascular endothelium is critically involved in the hypotensive and hypovolemic actions of atrial natriuretic peptide. Sabrane, K., Kruse, M.N., Fabritz, L., Zetsche, B., Mitko, D., Skryabin, B.V., Zwiener, M., Baba, H.A., Yanagisawa, M., Kuhn, M. J. Clin. Invest. (2005) [Pubmed]
  6. Renal C-type natriuretic peptide and natriuretic peptide receptor B mRNA expression are affected by water deprivation in the Spinifex Hopping mouse. Heimeier, R.A., Donald, J.A. Comp. Biochem. Physiol., Part A Mol. Integr. Physiol. (2003) [Pubmed]
  7. Salt-resistant hypertension in mice lacking the guanylyl cyclase-A receptor for atrial natriuretic peptide. Lopez, M.J., Wong, S.K., Kishimoto, I., Dubois, S., Mach, V., Friesen, J., Garbers, D.L., Beuve, A. Nature (1995) [Pubmed]
  8. Enhanced activity of the myocardial Na+/H+ exchanger NHE-1 contributes to cardiac remodeling in atrial natriuretic peptide receptor-deficient mice. Kilic, A., Velic, A., De Windt, L.J., Fabritz, L., Voss, M., Mitko, D., Zwiener, M., Baba, H.A., van Eickels, M., Schlatter, E., Kuhn, M. Circulation (2005) [Pubmed]
  9. Androgen contributes to gender-related cardiac hypertrophy and fibrosis in mice lacking the gene encoding guanylyl cyclase-A. Li, Y., Kishimoto, I., Saito, Y., Harada, M., Kuwahara, K., Izumi, T., Hamanaka, I., Takahashi, N., Kawakami, R., Tanimoto, K., Nakagawa, Y., Nakanishi, M., Adachi, Y., Garbers, D.L., Fukamizu, A., Nakao, K. Endocrinology (2004) [Pubmed]
  10. Role of natriuretic peptide receptor guanylyl cyclase-A in myocardial infarction evaluated using genetically engineered mice. Nakanishi, M., Saito, Y., Kishimoto, I., Harada, M., Kuwahara, K., Takahashi, N., Kawakami, R., Nakagawa, Y., Tanimoto, K., Yasuno, S., Usami, S., Li, Y., Adachi, Y., Fukamizu, A., Garbers, D.L., Nakao, K. Hypertension (2005) [Pubmed]
  11. Natriuretic peptide receptor 1 expression influences blood pressures of mice in a dose-dependent manner. Oliver, P.M., John, S.W., Purdy, K.E., Kim, R., Maeda, N., Goy, M.F., Smithies, O. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  12. Characterization of a cGMP-response element in the guanylyl cyclase/natriuretic peptide receptor A gene promoter. Hum, D., Besnard, S., Sanchez, R., Devost, D., Gossard, F., Hamet, P., Tremblay, J. Hypertension (2004) [Pubmed]
  13. Increased atherosclerosis and smooth muscle cell hypertrophy in natriuretic peptide receptor A-/-apolipoprotein E-/- mice. Alexander, M.R., Knowles, J.W., Nishikimi, T., Maeda, N. Arterioscler. Thromb. Vasc. Biol. (2003) [Pubmed]
  14. The guanylyl cyclase-deficient mouse defines differential pathways of natriuretic peptide signaling. Lopez, M.J., Garbers, D.L., Kuhn, M. J. Biol. Chem. (1997) [Pubmed]
  15. Evidence for a novel natriuretic peptide receptor that prefers brain natriuretic peptide over atrial natriuretic peptide. Goy, M.F., Oliver, P.M., Purdy, K.E., Knowles, J.W., Fox, J.E., Mohler, P.J., Qian, X., Smithies, O., Maeda, N. Biochem. J. (2001) [Pubmed]
  16. Guanylyl cyclase-A inhibits angiotensin II type 1A receptor-mediated cardiac remodeling, an endogenous protective mechanism in the heart. Li, Y., Kishimoto, I., Saito, Y., Harada, M., Kuwahara, K., Izumi, T., Takahashi, N., Kawakami, R., Tanimoto, K., Nakagawa, Y., Nakanishi, M., Adachi, Y., Garbers, D.L., Fukamizu, A., Nakao, K. Circulation (2002) [Pubmed]
  17. 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]
  18. Increased effects of C-type natriuretic peptide on cardiac ventricular contractility and relaxation in guanylyl cyclase A-deficient mice. Pierkes, M., Gambaryan, S., Bokník, P., Lohmann, S.M., Schmitz, W., Potthast, R., Holtwick, R., Kuhn, M. Cardiovasc. Res. (2002) [Pubmed]
  19. Vascular natriuretic peptide receptor-linked particulate guanylate cyclases are modulated by nitric oxide-cyclic GMP signalling. Madhani, M., Scotland, R.S., MacAllister, R.J., Hobbs, A.J. Br. J. Pharmacol. (2003) [Pubmed]
  20. Alternative splicing of the guanylyl cyclase-A receptor modulates atrial natriuretic peptide signaling. Hartmann, M., Skryabin, B.V., Müller, T., Gazinski, A., Schröter, J., Gassner, B., Nikolaev, V.O., Bünemann, M., Kuhn, M. J. Biol. Chem. (2008) [Pubmed]
  21. Reduced cGMP signaling activates NF-kappaB in hypertrophied hearts of mice lacking natriuretic peptide receptor-A. Vellaichamy, E., Sommana, N.K., Pandey, K.N. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  22. Essential biochemistry and physiology of (NT-pro)BNP. Hall, C. Eur. J. Heart Fail. (2004) [Pubmed]
  23. Transcriptional regulation of guanylyl cyclase/natriuretic peptide receptor-A gene. Kumar, P., Arise, K.K., Pandey, K.N. Peptides (2006) [Pubmed]
  24. Diverging vasorelaxing effects of C-type natriuretic peptide in renal resistance arteries and aortas of GC-A-deficient mice. Steinmetz, M., Potthast, R., Sabrane, K., Kuhn, M. Regul. Pept. (2004) [Pubmed]
  25. 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]
  26. Ventricular arrhythmias, increased cardiac calmodulin kinase II expression, and altered repolarization kinetics in ANP receptor deficient mice. Kirchhof, P., Fabritz, L., Kilić, A., Begrow, F., Breithardt, G., Kuhn, M. J. Mol. Cell. Cardiol. (2004) [Pubmed]
  27. Blockade of the natriuretic peptide receptor guanylyl cyclase-A inhibits NF-kappaB activation and alleviates myocardial ischemia/reperfusion injury. Izumi, T., Saito, Y., Kishimoto, I., Harada, M., Kuwahara, K., Hamanaka, I., Takahashi, N., Kawakami, R., Li, Y., Takemura, G., Fujiwara, H., Garbers, D.L., Mochizuki, S., Nakao, K. J. Clin. Invest. (2001) [Pubmed]
  28. AlbuBNP, a recombinant B-type natriuretic peptide and human serum albumin fusion hormone, as a long-term therapy of congestive heart failure. Wang, W., Ou, Y., Shi, Y. Pharm. Res. (2004) [Pubmed]
  29. Effects of different natriuretic peptides on nitric oxide synthesis in macrophages. Kiemer, A.K., Vollmar, A.M. Endocrinology (1997) [Pubmed]
  30. C-type natriuretic peptide/guanylate cyclase B system in ATDC5 cells, a chondrogenic cell line. Suda, M., Tanaka, K., Yasoda, A., Komatsu, Y., Chusho, H., Miura, M., Tamura, N., Ogawa, Y., Nakao, K. J. Bone Miner. Metab. (2002) [Pubmed]
  31. A genetic model defines the importance of the atrial natriuretic peptide receptor (guanylyl cyclase-A) in the regulation of kidney function. Dubois, S.K., Kishimoto, I., Lillis, T.O., Garbers, D.L. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  32. Differential expression and autoradiographic localization of atrial natriuretic peptide receptor in spontaneously hypertensive and normotensive rat testes: diminution of testosterone in hypertension. Kapasi, A.A., Kumar, R., Pauly, J.R., Pandey, K.N. Hypertension (1996) [Pubmed]
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