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Gene Review

Npr2  -  natriuretic peptide receptor 2

Rattus norvegicus

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

  • Guanosine 3',5'-cyclic monophosphate levels generated by NPR-A in renal papillae and by NPR-A and NPR-B in the adrenal cortex, aorta, and mesenteric arteries of DOCA-salt-treated rats remained increased in hypertension [1].
  • Hearts were then isolated and subjected to a zero-flow ischemia and reperfusion (except controls), in the absence or presence of either a B2-receptor antagonist (Hoe-140), a B1-receptor antagonist (Lys-Leu8-des-Arg9-BK), or the GC-A/GC-B-receptor antagonist (HS-142-1) [2].
  • Renal inner medulla GC-B mRNA levels, but not renal CNP mRNA levels, were 3.2-fold greater in hypervolemic and 2.3-fold less in hypovolemic rats compared with euvolemic controls [3].
  • The results indicate that there is a differential distribution of NPRs in the cardiac chambers, with the most abundant binding sites in RV endocardium, that NPR-B is the predominant GC-coupled NPR in ventricular endocardium, and that endocardial NPRs are downregulated with ventricular hypertrophy [4].

Psychiatry related information on Npr2

  • Water deprivation significantly decreased the relative levels of CNP and NPR-B mRNA expression in both the 7- and 14-day water-deprived hopping mice, when compared to control hopping mice [5].
  • The observed cross-talk of the PACAP/VIP receptors with GC-B but not with sGC may have implications for the therapy of erectile dysfunction [6].

High impact information on Npr2

  • We show that a second guanylate cyclase/receptor (GC-B) exists, with distinctly different specificities for various natriuretic peptides [7].
  • The deduced amino acid sequence of GC-B is 78% identical with GC-A within the intracellular region, but 43% identical within the extracellular domain [7].
  • A cDNA clone encoding GC-B was isolated by low-stringency screening of a rat brain cDNA library using GC-A cDNA as a probe [7].
  • The most striking observation was the gradual disappearance of NPR-C transcripts (the putative "clearance" receptor) in all chambers; this was in marked contrast to the increase in mRNA levels for NPR-A and NPR-B (the guanylyl cyclase-linked receptors) [8].
  • Analysis by RT-PCR revealed the presence of transcripts for NPR-A as well as NPR-B and NPR-C [9].

Biological context of Npr2

  • Furthermore, our data show that in the rat renal microcirculation stimulation of NPR-B results in vasodilation only, whereas NPR-C does not mediate vascular responses [10].
  • The ANP antagonist A71915 (10(-9) to 10(-6)) induced moderate dilation in renal vessels possibly due to some agonistic activity on NPR-B, ANP-induced preglomerular vasodilation was attenuated by A71915 (10(-6)) to 36 +/- 6% of the initial response, whereas efferent vasoconstriction was completely abolished (-4 +/- 4% of initial response) [10].
  • Binding studies were performed on membranes of COS-1 cells transfected with expression plasmids for either rat natriuretic peptide receptor (NPR)-A, rat NPR-B, or bovine NPR-C [11].
  • Moreover, TSH treatment decreased C-type natriuretic peptide (CNP)-induced cGMP generation in FRTL-5 cells, suggesting a down-regulation of NPR-B [12].
  • The two forms of rat GC-B differ from each other only by 75bp deletion at 3'-flanking region of the putative transmembrane domain, the shorter form lacking the nucleotide binding site by the deletion [13].

Anatomical context of Npr2


Associations of Npr2 with chemical compounds

  • In contrast, the cell-permeable calcium chelator, BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester), abrogates the AVP-dependent desensitization of NPR-B, and ionomycin, a calcium ionophore, mimics the AVP effect [18].
  • Vasopressin-dependent inhibition of the C-type natriuretic peptide receptor, NPR-B/GC-B, requires elevated intracellular calcium concentrations [18].
  • However, oxidation of the Met17 residue into methionine sulfoxide reduces the affinity of the compound for NPR-B by > 10-fold, whereas the addition of one or two iodines did not further reduce its affinity [11].
  • Semiquantitative RT-PCR revealed that granulosa cells from DES- or eCG-treated animals have increased levels of NPR-B messenger RNA (mRNA) transcripts, which was in good agreement with the increased binding [19].
  • To further understand the molecular significance of these regulations, we measured the relative abundance of the transcripts of NPR-A and NPR-B by Northern blot in the aorta, mesenteric arteries, adrenal cortex, renal papillae, and lungs in DOCA-salt hypertensive and control rats [1].

Other interactions of Npr2

  • Previous reports have shown that pressor hormones inhibit natriuretic peptide receptors NPR-A or NPR-B in a variety of different cell types [18].
  • The purpose of the present study was to determine whether TSH treatment, therefore, results in higher levels of ANF-induced intracellular cGMP, and whether TSH elicits similar effects on cGMP signaling through the NPR-B receptor [12].
  • TGF-beta 1 decreased both NPR-A and NPR-B mRNA levels with a predominant effect in SHR cells at high cell density.(ABSTRACT TRUNCATED AT 250 WORDS)[20]

Analytical, diagnostic and therapeutic context of Npr2

  • To define further the potential domains of ANP and CNP action in brain, the present study used in situ hybridization histochemistry to map NPR-A and NPR-B mRNA-expressing cell populations [21].
  • Radioimmunoassay and RNase protection analyses revealed passage-associated increase in CNP-like immunoreactivity and in levels of NPR-B mRNA, respectively [22].
  • Using a semi-quantitative multiplex PCR technique, the expression of renal CNP and NPR-B mRNA was determined in 7- and 14-day water-deprived hopping mice, in parallel with control hopping mice (access to water) [5].
  • GC-A and GC-B receptors were detected using quantitative autoradiography after application of either [125I]ANP or [125I]-tyr0CNP to sections of frozen ovaries [23].
  • These results indicate that GC-B, CNP specific receptor/guanylyl cyclase, is expressed at the sites of vascular injury, and that CNP might be efficacious in the prevention of restenosis caused by intimal thickening following coronary angioplasty [24].


  1. Gene expression of natriuretic peptide receptors in rats with DOCA-salt hypertension. Nuglozeh, E., Mbikay, M., Stewart, D.J., Legault, L. Am. J. Physiol. (1997) [Pubmed]
  2. The cardioprotective effect of dual metallopeptidase inhibition: respective roles of endogenous kinins and natriuretic peptides. Dumoulin, M.J., Adam, A., Burnett, J., Heublein, D., Yamaguchi, N., Lamontagne, D. Can. J. Physiol. Pharmacol. (2005) [Pubmed]
  3. Distribution and regulation of guanylyl cyclase type B in the rat nephron. Dean, A.D., Vehaskari, V.M., Ritter, D., Greenwald, J.E. Am. J. Physiol. (1996) [Pubmed]
  4. Modulation of endocardial natriuretic peptide receptors in right ventricular hypertrophy. Kim, S.Z., Cho, K.W., Kim, S.H. Am. J. Physiol. (1999) [Pubmed]
  5. 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]
  6. Characterization of VIP and PACAP receptors in cultured rat penis corpus cavernosum smooth muscle cells and their interaction with guanylate cyclase-B receptors. Guidone, G., Müller, D., Vogt, K., Mukhopadhyay, A.K. Regul. Pept. (2002) [Pubmed]
  7. The primary structure of a plasma membrane guanylate cyclase demonstrates diversity within this new receptor family. Schulz, S., Singh, S., Bellet, R.A., Singh, G., Tubb, D.J., Chin, H., Garbers, D.L. Cell (1989) [Pubmed]
  8. 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]
  9. Gene expression of natriuretic peptide receptors in myocardial cells. Lin, X., Hänze, J., Heese, F., Sodmann, R., Lang, R.E. Circ. Res. (1995) [Pubmed]
  10. Natriuretic peptide receptors mediate different responses in rat renal microvessels. Endlich, K., Steinhausen, M. Kidney Int. (1997) [Pubmed]
  11. Reduced affinity of iodinated forms of Tyr0 C-type natriuretic peptide for rat natriuretic peptide receptor B. Thibault, G., Grove, K.L., Deschepper, C.F. Mol. Pharmacol. (1995) [Pubmed]
  12. Regulation of natriuretic peptide receptors by thyrotropin in FRTL-5 rat thyroid cells: evidence for nonguanylate cyclase atrial natriuretic factor-binding sites in cells lacking the natriuretic peptide receptor C. Sellitti, D.F., Doi, S.Q. Endocrinology (1999) [Pubmed]
  13. Cloning and characterization of two forms of C-type natriuretic peptide receptor in rat brain. Ohyama, Y., Miyamoto, K., Saito, Y., Minamino, N., Kangawa, K., Matsuo, H. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  14. Immunolocalization of natriuretic peptide receptor B in the rat kidney. Bonhomme, M.C., Grove, K.L., Caron, S., Crilley, C.T., Thibault, G., Deschepper, C.F., Garcia, R. J. Am. Soc. Nephrol. (1998) [Pubmed]
  15. Tissue distribution and localization of natriuretic peptide receptor subtypes in stroke-prone spontaneously hypertensive rats. Nagase, M., Katafuchi, T., Hirose, S., Fujita, T. J. Hypertens. (1997) [Pubmed]
  16. C-type natriuretic Peptide down-regulates expression of its cognate receptor in rat aortic smooth muscle cells. Rahmutula, D., Gardner, D.G. Endocrinology (2005) [Pubmed]
  17. Natriuretic peptide receptor-B in adult rat ventricle is predominantly confined to the nonmyocyte population. Doyle, D.D., Upshaw-Earley, J., Bell, E.L., Palfrey, H.C. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  18. Vasopressin-dependent inhibition of the C-type natriuretic peptide receptor, NPR-B/GC-B, requires elevated intracellular calcium concentrations. Abbey, S.E., Potter, L.R. J. Biol. Chem. (2002) [Pubmed]
  19. B-type natriuretic peptide receptor expression and activity are hormonally regulated in rat ovarian cells. Noubani, A., Farookhi, R., Gutkowska, J. Endocrinology (2000) [Pubmed]
  20. Regulation of natriuretic peptide receptor A and B expression by transforming growth factor-beta 1 in cultured aortic smooth muscle cells. Fujio, N., Gossard, F., Bayard, F., Tremblay, J. Hypertension (1994) [Pubmed]
  21. Localization of natriuretic peptide-activated guanylate cyclase mRNAs in the rat brain. Herman, J.P., Dolgas, C.M., Rucker, D., Langub, M.C. J. Comp. Neurol. (1996) [Pubmed]
  22. Change in the expression of C-type natriuretic peptide and its receptor, B-type natriuretic peptide receptor, during dedifferentiation of chondrocytes into fibroblast-like cells. Hagiwara, H., Inoue, A., Furuya, M., Tanaka, S., Hirose, S. J. Biochem. (1996) [Pubmed]
  23. C-type natriuretic peptide and the guanylyl cyclase receptors in the rat ovary are modulated by the estrous cycle. Jankowski, M., Reis, A.M., Mukaddam-Daher, S., Dam, T.V., Farookhi, R., Gutkowska, J. Biol. Reprod. (1997) [Pubmed]
  24. C-type natriuretic peptide inhibits intimal thickening after vascular injury. Furuya, M., Aisaka, K., Miyazaki, T., Honbou, N., Kawashima, K., Ohno, T., Tanaka, S., Minamino, N., Kangawa, K., Matsuo, H. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
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