The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

NPPA  -  natriuretic peptide A

Homo sapiens

Synonyms: ANF, ANP, ATFB6, ATRST2, CDD, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of NPPA


Psychiatry related information on NPPA

  • Further studies to assess ANP secretion in PTSD patients and to clarify its pathophysiological impact are needed [5].
  • Using hybridization analysis, we further show that the amount of rat preproCDD-ANF mRNA, which is synthesized selectively in the atria but not the ventricles, markedly decreases on water deprivation, suggesting that the water-electrolyte balance may be an important factor in the regulation of the expression of the preproCDD-ANF gene [6].
  • Atrial natriuretic peptide (ANP) is causally involved in sodium lactate-induced panic attacks [7].
  • Furthermore, preclinical and clinical data on its anxiolytic activity suggest that non-peptidergic ANP receptor ligands may be of potential use in the treatment of anxiety disorders [7].
  • AVP and ANP levels have been found to be abnormal in a range of stress disorders and psychiatric illnesses [8].

High impact information on NPPA

  • ANP is mostly localized in the heart, but ANP and its receptor are also found in hypothalamic and brain stem areas involved in body fluid volume and blood pressure regulation [9].
  • Angiotensin II also plays an important role in the regulation of body fluids, being a potent inducer of thirst and, in general, antagonizes the actions of ANP [9].
  • This review emphasizes the role played by brain ANP and its interaction with neurohypophysial hormones in the control of body fluid homeostasis [9].
  • Blood volume expansion acts not only directly on the heart, by stretch of atrial myocytes to increase the release of ANP, but also on the brain ANPergic neurons through afferent inputs from baroreceptors [9].
  • For example, in the rat, OT is a cardiovascular hormone acting in concert with atrial natriuretic peptide to induce natriuresis and kaliuresis [10].

Chemical compound and disease context of NPPA


Biological context of NPPA


Anatomical context of NPPA

  • In cardiac myocytes, ANP is synthesized as a precursor, pro-ANP, that is converted to biologically active ANP by an unknown membrane-associated protease [18].
  • Reverse transcription-PCR detected corin mRNA expression in all nine SCLC cell lines examined and ANP mRNA expression in seven of the nine cell lines [2].
  • ANP-treated macrophages displayed decreased TNF-alpha-mRNA levels [20].
  • In this study, we explored the possibility that ANP and GC-A may play a role in the dendritic cell (DC)-mediated immune regulation [19].
  • In accordance with this change of cytokine production, DCs treated with ANP plus LPS promoted differentiation of naive CD4(+) T cells into a Th2 phenotype [19].

Associations of NPPA with chemical compounds


Physical interactions of NPPA

  • Hence, from a thematic standpoint it is clearly evident that there is a current need to review this subject and provide a consensus forum that establishes the cellular trafficking, sequestration and processing of ANP/NPRA complexes in intact cells [23].
  • Natriuretic peptide receptor C (NPR-C) mRNA expression and ANP-binding activity via NPR-C are significantly down-regulated in HeLa cells with phorbol myristate acetate (PMA) treatment [24].
  • The regulation of AQP1 ion channels could be one of several transport mechanisms that contribute to the decreased CSF secretion in response to endogenous signaling molecules such as atrial natriuretic peptide [25].
  • Two pathways of clearance for atrial natriuretic peptide are recognized: degradation by neutral endopeptidase and binding to atrial natriuretic peptide clearance receptors [26].
  • Both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) bind preferentially to the natriuretic peptide A receptor [27].

Enzymatic interactions of NPPA

  • Significant increases in retracted cell number were induced by ANF and CNP, but not the NPR-C-specific ring-deleted ANF analog, C-ANF(4-23), during a 15-day treatment [28].
  • Recently, we identified six phosphorylation sites within the kinase homology domain of NPR-A and determined that the conversion of these residues to alanine abolished the ability of the receptor to be phosphorylated or to be activated by ANP and ATP [29].
  • Both neprilysin and metalloendopeptidase 24.15 form Ang-(1-7) but also cleave bradykinin and atrial natriuretic peptide to smaller fragments [30].

Regulatory relationships of NPPA


Other interactions of NPPA

  • CRH also caused acute activation of the membrane-bound GC, shown by increased basal or atrial natriuretic peptide (ANP)-stimulated cGMP production [36].
  • In this study, we examine effects of corin on pro-ANP processing [18].
  • HS-142-1 also enhanced dissociation of NPR-A-bound (125)I-ANP in the presence of excess unlabelled ANP, implying an allotopic (allosteric) mode of action for the antagonist [37].
  • Moreover, all assessed ANP effects seem to be mediated by the NPR-C [38].
  • Pretreatment of human umbilical vein endothelial cells (HUVEC) with ANP significantly reduced TNF-alpha-induced expression of MCP-1 protein and mRNA [39].

Analytical, diagnostic and therapeutic context of NPPA

  • This location coincided with that of the NPPA locus; pulsed-field gel electrophoresis placed NPPA and NPPB within 50 kb of each other [40].
  • To investigate the underlying mechanism of ANP-mediated TNF-alpha inhibition, Northern blot was performed [20].
  • CONCLUSION: Plasma mAM reflects cardiac dysfunction, excessive blood volume, and inflammation better than ANP, BNP, and NE, resulting in a predictor of mortality and cardiovascular morbidity in hemodialysis patients with cardiovascular disease [41].
  • RESULTS: ADM (27.2+/-4.1 vs. 53.8+/-6.9 pmol/l, P=0.02), and ANP (5.9+/-0.9 vs. 12.8+/-1.4 pmol/l, P=0.001) were significantly increased in late, stable Ltx (35.4+/-9.6 months after transplantation) [42].
  • The expression of ANP and its receptors was analyzed by RT-PCR [43].


  1. Production of an atrial natriuretic peptide variant that is specific for type A receptor. Cunningham, B.C., Lowe, D.G., Li, B., Bennett, B.D., Wells, J.A. EMBO J. (1994) [Pubmed]
  2. Corin-mediated processing of pro-atrial natriuretic peptide in human small cell lung cancer cells. Wu, F., Wu, Q. Cancer Res. (2003) [Pubmed]
  3. Influence of exogenous atrial natriuretic peptide on the pituitary-adrenal response to corticotropin-releasing hormone and vasopressin in healthy men. Bierwolf, C., Burgemeister, A., Lüthke, K., Born, J., Fehm, H.L. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  4. Effect of plasma osmolality on pituitary-adrenal responses to corticotropin-releasing hormone and atrial natriuretic peptide changes in central diabetes insipidus. Elias, L.L., Antunes-Rodrigues, J., Elias, P.C., Moreira, A.C. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  5. Endocrine and cardiovascular responses to corticotropin-releasing hormone in patients with posttraumatic stress disorder: a role for atrial natriuretic peptide? Kellner, M., Yassouridis, A., Hübner, R., Baker, D.G., Wiedemann, K. Neuropsychobiology (2003) [Pubmed]
  6. mRNA sequence for human cardiodilatin-atrial natriuretic factor precursor and regulation of precursor mRNA in rat atria. Nakayama, K., Ohkubo, H., Hirose, T., Inayama, S., Nakanishi, S. Nature (1984) [Pubmed]
  7. Stress responsive neurohormones in depression and anxiety. Ströhle, A., Holsboer, F. Pharmacopsychiatry (2003) [Pubmed]
  8. Stress and water balance: the roles of ANP, AVP and isatin. Bhattacharya, S.K., Chakrabarti, A., Glover, V. Indian J. Exp. Biol. (1998) [Pubmed]
  9. Neuroendocrine control of body fluid metabolism. Antunes-Rodrigues, J., de Castro, M., Elias, L.L., Valença, M.M., McCann, S.M. Physiol. Rev. (2004) [Pubmed]
  10. The oxytocin receptor system: structure, function, and regulation. Gimpl, G., Fahrenholz, F. Physiol. Rev. (2001) [Pubmed]
  11. Circulating adrenomedullin is increased after heart transplantation. Geny, B., Brandenberger, G., Lonsdorfer, J., Chakfé, N., Haberey, P., Piquard, F. Cardiovasc. Res. (1999) [Pubmed]
  12. Intracerebroventricular administration of atrial natriuretic peptide prevents increase of plasma ADH, aldosterone and corticosterone levels in restrained conscious dehydrated rabbits. Kallaras, C., Angelopoulos, N., Bountzioukas, S., Mavroudis, K., Karamouzis, M., Guiba-Tziampiri, O. J. Endocrinol. Invest. (2004) [Pubmed]
  13. Atrial natriuretic peptide-C receptor and membrane signalling in hypertension. Anand-Srivastava, M.B. J. Hypertens. (1997) [Pubmed]
  14. Relaxin antagonizes hypertrophy and apoptosis in neonatal rat cardiomyocytes. Moore, X.L., Tan, S.L., Lo, C.Y., Fang, L., Su, Y.D., Gao, X.M., Woodcock, E.A., Summers, R.J., Tregear, G.W., Bathgate, R.A., Du, X.J. Endocrinology (2007) [Pubmed]
  15. Renal atrial natriuretic peptide receptors binding properties and function are resistant to DOCA-salt-induced hypertension in rats. Woodard, G.E., Li, X., Rosado, J.A. Regul. Pept. (2007) [Pubmed]
  16. Selected gene polymorphisms and their interaction with maternal smoking, as risk factors for gastroschisis. Torfs, C.P., Christianson, R.E., Iovannisci, D.M., Shaw, G.M., Lammer, E.J. Birth Defects Res. Part A Clin. Mol. Teratol. (2006) [Pubmed]
  17. Novel analog of atrial natriuretic peptide selective for receptor-A produces increased diuresis and natriuresis in rats. Jin, H., Li, B., Cunningham, B., Tom, J., Yang, R., Sehl, P., Thomas, G.R., Ko, A., Oare, D., Lowe, D.G. J. Clin. Invest. (1996) [Pubmed]
  18. Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme. Yan, W., Wu, F., Morser, J., Wu, Q. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  19. Atrial natriuretic peptide polarizes human dendritic cells toward a Th2-promoting phenotype through its receptor guanylyl cyclase-coupled receptor A. Morita, R., Ukyo, N., Furuya, M., Uchiyama, T., Hori, T. J. Immunol. (2003) [Pubmed]
  20. cGMP-mediated inhibition of TNF-alpha production by the atrial natriuretic peptide in murine macrophages. Kiemer, A.K., Hartung, T., Vollmar, A.M. J. Immunol. (2000) [Pubmed]
  21. Induction and reversal of cardiac phenotype of human hypertrophic cardiomyopathy mutation cardiac troponin T-Q92 in switch on-switch off bigenic mice. Lutucuta, S., Tsybouleva, N., Ishiyama, M., Defreitas, G., Wei, L., Carabello, B., Marian, A.J. J. Am. Coll. Cardiol. (2004) [Pubmed]
  22. cGMP-dependent and -independent inhibition of a K+ conductance by natriuretic peptides: molecular and functional studies in human proximal tubule cells. Hirsch, J.R., Meyer, M., Mägert, H.J., Forssmann, W.G., Mollerup, S., Herter, P., Weber, G., Cermak, R., Ankorina-Stark, I., Schlatter, E., Kruhøffer, M. J. Am. Soc. Nephrol. (1999) [Pubmed]
  23. Intracellular trafficking and metabolic turnover of ligand-bound guanylyl cyclase/atrial natriuretic peptide receptor-A into subcellular compartments. Pandey, K.N. Mol. Cell. Biochem. (2002) [Pubmed]
  24. Protein kinase C activation down-regulates natriuretic peptide receptor C expression via transcriptional and post-translational pathways. Yanaka, N., Akatsuka, H., Omori, K. FEBS Lett. (1997) [Pubmed]
  25. Physiological roles of aquaporins in the choroid plexus. Boassa, D., Yool, A.J. Curr. Top. Dev. Biol. (2005) [Pubmed]
  26. Clearance of brain natriuretic peptide in patients with chronic heart failure: indirect evidence for a neutral endopeptidase mechanism but against an atrial natriuretic peptide clearance receptor mechanism. Lang, C.C., Motwani, J.G., Coutie, W.J., Struthers, A.D. Clin. Sci. (1992) [Pubmed]
  27. Effects of human atrial natriuretic peptide on cardiac function and hemodynamics in patients with high plasma BNP levels. Nakajima, K., Onishi, K., Dohi, K., Tanabe, M., Kurita, T., Yamanaka, T., Ito, M., Isaka, N., Nobori, T., Nakano, T. International journal of cardiology. (2005) [Pubmed]
  28. Atrial natriuretic factor and C-type natriuretic peptide induce retraction of human thyrocytes in monolayer culture via guanylyl cyclase receptors. Sellitti, D.F., Lagranha, C., Perrella, G., Curcio, F., Doi, S.Q. J. Endocrinol. (2002) [Pubmed]
  29. A constitutively "phosphorylated" guanylyl cyclase-linked atrial natriuretic peptide receptor mutant is resistant to desensitization. Potter, L.R., Hunter, T. Mol. Biol. Cell (1999) [Pubmed]
  30. Angiotension-(1-7) and antihypertensive mechanisms. Ferrario, C.M. J. Nephrol. (1998) [Pubmed]
  31. Differential gene expression of the three natriuretic peptides and natriuretic peptide receptor subtypes in human liver. Vollmar, A.M., Paumgartner, G., Gerbes, A.L. Gut (1997) [Pubmed]
  32. Down-regulation does not mediate natriuretic peptide-dependent desensitization of natriuretic peptide receptor (NPR)-A or NPR-B: guanylyl cyclase-linked natriuretic peptide receptors do not internalize. Fan, D., Bryan, P.M., Antos, L.K., Potthast, R.J., Potter, L.R. Mol. Pharmacol. (2005) [Pubmed]
  33. Adrenomedullin stimulates cAMP accumulation and inhibits atrial natriuretic peptide gene expression in cardiomyocytes. Sato, A., Canny, B.J., Autelitano, D.J. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  34. Localization of the mosaic transmembrane serine protease corin to heart myocytes. Hooper, J.D., Scarman, A.L., Clarke, B.E., Normyle, J.F., Antalis, T.M. Eur. J. Biochem. (2000) [Pubmed]
  35. Effect of corticotrophin-releasing hormone on arginine vasopressin and atrial natriuretic factor in patients with Cushing's disease. Colao, A., Pivonello, R., Ferone, D., Faggiano, A., Facciolli, G., Di Somma, C., Boudouresque, F., Oliver, C., Lombardi, G. Clin. Endocrinol. (Oxf) (1998) [Pubmed]
  36. Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells. Aggelidou, E., Hillhouse, E.W., Grammatopoulos, D.K. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  37. Allotopic antagonism of the non-peptide atrial natriuretic peptide (ANP) antagonist HS-142-1 on natriuretic peptide receptor NPR-A. Poirier, H., Labrecque, J., Deschênes, J., DeLéan, A. Biochem. J. (2002) [Pubmed]
  38. Differential sensitivity of human monocytes and macrophages to ANP: a role of intracellular pH on reactive oxygen species production through the phospholipase involvement. Baldini, P.M., De Vito, P., Martino, A., Fraziano, M., Grimaldi, C., Luly, P., Zalfa, F., Colizzi, V. J. Leukoc. Biol. (2003) [Pubmed]
  39. ANP inhibits TNF-alpha-induced endothelial MCP-1 expression--involvement of p38 MAPK and MKP-1. Weber, N.C., Blumenthal, S.B., Hartung, T., Vollmar, A.M., Kiemer, A.K. J. Leukoc. Biol. (2003) [Pubmed]
  40. Localization of the human B-type natriuretic peptide precursor (NPPB) gene to chromosome 1p36. Arden, K.C., Viars, C.S., Weiss, S., Argentin, S., Nemer, M. Genomics (1995) [Pubmed]
  41. Adrenomedullin reflects cardiac dysfunction, excessive blood volume, and inflammation in hemodialysis patients. Yoshihara, F., Horio, T., Nakamura, S., Yoshii, M., Ogata, C., Nakahama, H., Inenaga, T., Kangawa, K., Kawano, Y. Kidney Int. (2005) [Pubmed]
  42. Circulating adrenomedullin is increased in relation with increased creatinine and atrial natriuretic peptide in liver-transplant recipients. Geny, B., Ellero, B., Charloux, A., Brandenberger, G., Doutreleau, S., Piquard, F. Regul. Pept. (2003) [Pubmed]
  43. 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]
WikiGenes - Universities