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Gene Review

NPPB  -  natriuretic peptide B

Homo sapiens

Synonyms: Gamma-brain natriuretic peptide, Natriuretic peptides B
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Disease relevance of NPPB

  • Furosemide and NPPB blocked the outward-rectifying lactate current and the sorbitol hemolysis with IC(50)s in the range of 0.1 and 1 microM, respectively [1].
  • Replacement of intracellular Cl- by impermeant anions, as well as treatment of insulinoma cells by the Cl- channel blocker, NPPB, leads to activation of ATP-dependent K+ (KATP) channels [2].
  • Therefore, arterial hypotension may be a necessary but not sufficient condition for the development of "steal" and NPPB [3].
  • Control of hemorrhage during AVM surgery is one of the key issues to prevent NPPB [4].

High impact information on NPPB

  • The capability to inhibit GCAC1 increases in a dose-dependent manner in the sequence: probenecid less than A-9-C less than ethacrynic acid less than niflumic acid less than IAA-94 less than NPPB [5].
  • 1) In PANC-1 cells, cAMP causes parallel activation of Cl- channels and of HCO3- extrusion by DIDS-sensitive and Na+-independent Cl-/HCO3- exchange, both effects being inhibited by Cl- channel blockers NPPB and glibenclamide [6].
  • Long-term (70 days) induced expression increased COL1A1 and COL1A3 mRNAs levels and collagen volume fraction and reduced levels of NPPA and NPPB [7].
  • In contrast, the IC(50)s of NPPB and furosemide for the inward-rectifying current were >10 microM [1].
  • GaCl was not affected by the putative Cl- channel blockers Cu2+, DIDS, DNDS, DPC, furosemide, IAA-94, MK-196, NPPB, SITS, verapamil, and glibenclamide [8].

Biological context of NPPB


Anatomical context of NPPB


Associations of NPPB with chemical compounds


Regulatory relationships of NPPB

  • These results indicate that both NPPB and DPC block CFTR by entering the pore from the cytoplasmic side and that the structural requirements for binding are not the same, although the binding regions within the pore are similar [13].
  • NPPB inhibited VIP-stimulated Cl- uptake into T84 cells with an IC50 of 414 microM [21].

Other interactions of NPPB


Analytical, diagnostic and therapeutic context of NPPB

  • This location coincided with that of the NPPA locus; pulsed-field gel electrophoresis placed NPPA and NPPB within 50 kb of each other [9].
  • In the case of small AVMs, surgery alone is a viable option; however, in the case of large AVMs, pre-operative embolisation is essential for prevention of NPPB (normal perfusion pressure breakthrough) [27].


  1. Organic osmolyte permeabilities of the malaria-induced anion conductances in human erythrocytes. Duranton, C., Huber, S.M., Tanneur, V., Brand, V.B., Akkaya, C., Shumilina, E.V., Sandu, C.D., Lang, F. J. Gen. Physiol. (2004) [Pubmed]
  2. ATP-sensitive K+ channels reveal the effects of intracellular chloride variations on cytoplasmic ATP concentrations and mitochondrial function. de Weille, J.R., Lazdunski, M. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  3. The effects of intracranial arteriovenous malformations on cerebral hemodynamics. Kader, A., Young, W.L. Neurosurg. Clin. N. Am. (1996) [Pubmed]
  4. Control of hemorrhage during AVM surgery--with special reference to treatment of dilated capillaries and arteries around the nidus. Kato, Y., Sano, H., Nagahisa, S., Yoshimoto, J., Ninomiya, T., Kanaoka, N., Kanno, T. Minimally invasive neurosurgery : MIN. (1998) [Pubmed]
  5. Identification and modulation of a voltage-dependent anion channel in the plasma membrane of guard cells by high-affinity ligands. Marten, I., Zeilinger, C., Redhead, C., Landry, D.W., al-Awqati, Q., Hedrich, R. EMBO J. (1992) [Pubmed]
  6. Ca2+-activated Cl- channels can substitute for CFTR in stimulation of pancreatic duct bicarbonate secretion. Zsembery, A., Strazzabosco, M., Graf, J. FASEB J. (2000) [Pubmed]
  7. 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]
  8. cAMP-activated apical membrane chloride channels in Necturus gallbladder epithelium. Conductance, selectivity, and block. Copello, J., Heming, T.A., Segal, Y., Reuss, L. J. Gen. Physiol. (1993) [Pubmed]
  9. 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]
  10. Voltage-dependent membrane currents of cultured human neurofibromatosis type 2 Schwann cells. Kamleiter, M., Hanemann, C.O., Kluwe, L., Rosenbaum, C., Wosch, S., Mautner, V.F., Müller, H.W., Grafe, P. Glia (1998) [Pubmed]
  11. K+ channel block-induced mammalian neuroblastoma cell swelling: a possible mechanism to influence proliferation. Rouzaire-Dubois, B., Dubois, J.M. J. Physiol. (Lond.) (1998) [Pubmed]
  12. Cl- channel inhibitors of the arylaminobenzoate type act as photosystem II herbicides: a functional and structural study. Bock, A., Krieger-Liszkay, A., Beitia Ortiz de Zarate, I., Schönknecht, G. Biochemistry (2001) [Pubmed]
  13. Direct comparison of NPPB and DPC as probes of CFTR expressed in Xenopus oocytes. Zhang, Z.R., Zeltwanger, S., McCarty, N.A. J. Membr. Biol. (2000) [Pubmed]
  14. The chloride channel blocker 5-nitro-2-(3-phenylpropyl-amino) benzoic acid (NPPB) uncouples mitochondria and increases the proton permeability of the plasma membrane in phagocytic cells. Lukacs, G.L., Nanda, A., Rotstein, O.D., Grinstein, S. FEBS Lett. (1991) [Pubmed]
  15. Small-conductance chloride channels in human peripheral T lymphocytes. Schumacher, P.A., Sakellaropoulos, G., Phipps, D.J., Schlichter, L.C. J. Membr. Biol. (1995) [Pubmed]
  16. cAMP-induced chloride transport in NCL-SG3 sweat gland cells. Mörk, A.C., von Euler, A., Roomans, G.M., Ring, A. Acta Physiol. Scand. (1996) [Pubmed]
  17. cAMP-stimulated ion currents in Xenopus oocytes expressing CFTR cRNA. Cunningham, S.A., Worrell, R.T., Benos, D.J., Frizzell, R.A. Am. J. Physiol. (1992) [Pubmed]
  18. Interdependency of beta-adrenergic receptors and CFTR in regulation of alveolar active Na+ transport. Mutlu, G.M., Adir, Y., Jameel, M., Akhmedov, A.T., Welch, L., Dumasius, V., Meng, F.J., Zabner, J., Koenig, C., Lewis, E.R., Balagani, R., Traver, G., Sznajder, J.I., Factor, P. Circ. Res. (2005) [Pubmed]
  19. Characterization of a phosphorylation-activated Cl-selective channel in isolated Necturus enterocytes. Giraldez, F., Murray, K.J., Sepúlveda, F.V., Sheppard, D.N. J. Physiol. (Lond.) (1989) [Pubmed]
  20. Regulatory volume decrease is actively modulated during the cell cycle. Wang, L., Chen, L., Zhu, L., Rawle, M., Nie, S., Zhang, J., Ping, Z., Kangrong, C., Jacob, T.J. J. Cell. Physiol. (2002) [Pubmed]
  21. Effects of NPPB (5-nitro-2-(3-phenylpropylamino)benzoic acid) on chloride transport in intestinal tissues and the T84 cell line. Keeling, D.J., Taylor, A.G., Smith, P.L. Biochim. Biophys. Acta (1991) [Pubmed]
  22. Glutamate acts at NMDA receptors on fresh bovine and on cultured human retinal pigment epithelial cells to trigger release of ATP. Reigada, D., Lu, W., Mitchell, C.H. J. Physiol. (Lond.) (2006) [Pubmed]
  23. Functional characterization of wild-type and a mutated form of SLC26A4 identified in a patient with Pendred syndrome. Dossena, S., Vezzoli, V., Cerutti, N., Bazzini, C., Tosco, M., Sironi, C., Rodighiero, S., Meyer, G., Fascio, U., Fürst, J., Ritter, M., Fugazzola, L., Persani, L., Zorowka, P., Storelli, C., Beck-Peccoz, P., Bottà, G., Paulmichl, M. Cell. Physiol. Biochem. (2006) [Pubmed]
  24. Signaling and distribution of NPR-Bi, the human splice form of the natriuretic peptide receptor type B. Hirsch, J.R., Skutta, N., Schlatter, E. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  25. Suppression of cell proliferation with induction of p21 by Cl(-) channel blockers in human leukemic cells. Jiang, B., Hattori, N., Liu, B., Nakayama, Y., Kitagawa, K., Inagaki, C. Eur. J. Pharmacol. (2004) [Pubmed]
  26. Activation of transepithelial ion transport by secretin in human intestinal Caco-2 cells. Fukuda, M., Ohara, A., Bamba, T., Saek, Y. Jpn. J. Physiol. (2000) [Pubmed]
  27. Strategy for the treatment of arteriovenous malformations. Sano, H., Kato, Y., Bannur, U., Okuma, I., Kanaoka, N., Kanno, T. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. (2000) [Pubmed]
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