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Gene Review

BDKRB2  -  bradykinin receptor B2

Homo sapiens

Synonyms: B2 bradykinin receptor, B2R, BK-2, BK-2 receptor, BK2, ...
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Disease relevance of BDKRB2


High impact information on BDKRB2

  • BK-induced NF-kappaB activation correlated with IL-1beta message upregulation with respect to agonist concentration, time course, sensitivity to bacterial toxins, and blockade by the B2 receptor antagonist [6].
  • In additional 4 and 16-wk-old animals, bradykinin B1 and B2 receptor antagonists (BKA) were also injected with EB [7].
  • Allelic polymorphisms affecting exon 3 of the B1 receptor gene (A1098-->G) or exon 2 (C181-->T) or 1 (a 9-base pair deletion) of the B2 receptor gene were found to be neutral [8].
  • Incubation with norepinephrine or the alpha2-adrenergic agonist BHT 920 also caused dose-dependent increases in nitrite production, which were blocked by the B2-receptor antagonist HOE 140 [9].
  • We have made mutations in the predicted sixth transmembrane segment of a rat B2 bradykinin receptor and analyzed the variant proteins by expressing them in COS-1 cells [10].

Chemical compound and disease context of BDKRB2

  • OBJECTIVE: To identify variants in the complete genomic sequence of the two subtypes of bradykinin receptors: B1 (BDKRB1) and B2 (BDKRB2) and to examine the association of these variants with essential hypertension [1].
  • Identification of a B2-bradykinin receptor linked to phospholipase C and inhibition of dopamine stimulated cyclic AMP accumulation in the human astrocytoma cell line D384 [11].
  • After 4 weeks, the B2 receptor antagonist icatibant (0.5 mg/kg body weight) was administered on top of active treatment for 4 weeks to 50% of the TGRen2 rats [12].
  • In addition, the inducible NO synthase (iNOS) mRNA level increased markedly, and this was reduced by LF 16-0687 Ms. Taken together, these data support a detrimental role of B2R in the development of the neurological deficit and of the inflammatory secondary damage resulting from diffuse traumatic brain injury [13].
  • To determine whether kinins contribute to allergic reactions, the effect of a potent, nonpeptide BK B2-receptor-specific antagonist, FR173657, on VPE induced in the reaction sites was investigated [14].

Biological context of BDKRB2


Anatomical context of BDKRB2


Associations of BDKRB2 with chemical compounds

  • Structure and chromosomal localization of the gene (BDKRB2) encoding human bradykinin B2 receptor [20].
  • Activity was partially recovered by subsequent alanine mutation of a cluster of two serines and two threonines in IC-IV of either B1(B2ICIV) or B1(B2ICIV)A(121), a cluster that is important for B2R desensitization [21].
  • Steady-state absorbance spectra of nNOS recorded during uncoupled NADPH oxidation showed that the heme remained oxidized in the presence of the synthetic peptide consisting of amino acids 310-329 of the B2R, whereas the reduced oxyferrous heme complex was accumulated in its absence [22].
  • These data suggest that binding of the B2R 310-329 peptide blocks flavin to heme electron transfer [22].
  • Endothelial nitric-oxide synthase (type III) (eNOS) was reported to form an inhibitory complex with the bradykinin receptor B2 (B2R) from which the enzyme is released in an active form upon receptor activation (Ju, H., Venema, V. J., Marrero, M. B., and Venema, R. C. (1998) J. Biol. Chem. 273, 24025-24029) [22].

Physical interactions of BDKRB2

  • Interaction of endothelial and neuronal nitric-oxide synthases with the bradykinin B2 receptor. Binding of an inhibitory peptide to the oxygenase domain blocks uncoupled NADPH oxidation [22].
  • A prototypic study of the molecular mechanisms of activation or inactivation of peptide hormone G protein-coupled receptors was carried out on the human B2 bradykinin receptor [23].

Co-localisations of BDKRB2


Regulatory relationships of BDKRB2

  • In conclusion, this study shows that BK upregulates IL-1beta- and TNFalpha-stimulated IL-8 production via BK B2 receptor and that PKC signal pathway seems to be involved in the upregulation of the cytokine-induced IL-8 production in gingival fibroblasts [25].
  • The B2 receptor antagonist HOE140 and the B1 receptor agonist des-Arg9-bradykinin failed to induce significant phosphorylation of the B2 receptor [26].
  • Furthermore, the treatment of primary cultures of trigeminal ganglia with inhibitors of EP24.15/16 led to the potentiation of several bradykinin-induced events that occur downstream of B2R activation [27].
  • TNF-alpha and IL-1beta both induced a rapid and transient increase in B1 and B2 receptor mRNA expression that was maximal by 2 h, accompanied by an increase in B1 and B2 receptor protein, as measured by radioligand binding assay with [(3)H]des-Arg(10)-kallidin, and [(3)H]bradykinin, respectively [28].
  • Furthermore, increasing doses of this inhibitor partially affected the bradykinin-mediated ERK/MAP kinase activation and fully blocked the protein kinase C-independent component of the signaling pathway from the B2 receptor to the ERK/MAP kinase cascade [29].

Other interactions of BDKRB2

  • Selective immunoprecipitation with epitope-specific antibodies revealed a spontaneously formed heterologous receptor complex, which was composed of the intact 35-kDa B1R and the B2R degradation products [17].
  • Using a synthetic peptide derived from the known inhibitory sequence of the B2R (residues 310-329) we studied the interaction of the receptor with purified eNOS and neuronal nitric-oxide synthase (type I) (nNOS) [22].
  • The stimulatory effect of BK on the IL-1beta- or TNFalpha-stimulated IL-8 production was reduced in the presence of BK B2 receptor antagonist HOE 140, whereas the B1 receptor antagonist Lys-(des-arg9, Leu8)-BK had no effect [25].
  • Negative and positive regulatory epitopes in the C-terminal domains of the human B1 and B2 bradykinin receptor subtypes determine receptor coupling efficacy to G(q/11)-mediated [correction of G(9/11)-mediated] phospholipase Cbeta activity [30].
  • Low-molecular-weight kininogen and B2 receptor mRNAs were colocalized in the zona glomerulosa and zona fasciculata and also in the zona reticularis and chromaffin cells but to a lesser degree [31].

Analytical, diagnostic and therapeutic context of BDKRB2

  • The polymorphism (-58 T/C) in the promoter region of the BDKRB2 was determined using the TaqMan-polymerase chain reaction (PCR) method, the exon 1 +9/-9 polymorphism of the BDKRB2 and I/D polymorphism of the ACE were monitored by PCR and gel electrophoresis [2].
  • Co-immunoprecipitation of B2R and nNOS from human embryonic kidney cells stably transfected with human nNOS suggests that the B2R may functionally interact with nNOS in vivo [22].
  • Using surface plasmon resonance analysis, we observed that an immunoreceptor tyrosine-based inhibitory motif (ITIM) located in the C-terminal part of the B2 receptor interacted specifically with the protein-tyrosine phosphatase SHP-2 [32].
  • Previous works have shown a neuroprotector effect for kinin B2 receptor and a deleterious, pro-epileptogenic action for kinin B1 receptor in animal models of TLE [33].
  • CLR contained B2R and B1R as determined by both receptor immunoblotting and the increase in specific activity of receptor agonist binding to cells at both 4 and 37 degrees C when binding was followed by CLR enrichment [34].


  1. Sequence variation of bradykinin receptors B1 and B2 and association with hypertension. Cui, J., Melista, E., Chazaro, I., Zhang, Y., Zhou, X., Manolis, A.J., Baldwin, C.T., Destefano, A.L., Gavras, H. J. Hypertens. (2005) [Pubmed]
  2. Relationship of bradykinin B2 receptor gene polymorphism with essential hypertension and left ventricular hypertrophy. Fu, Y., Katsuya, T., Matsuo, A., Yamamoto, K., Akasaka, H., Takami, Y., Iwashima, Y., Sugimoto, K., Ishikawa, K., Ohishi, M., Rakugi, H., Ogihara, T. Hypertens. Res. (2004) [Pubmed]
  3. Immunolocalization and expression of kinin B1R and B2R receptors in human inflammatory bowel disease. Stadnicki, A., Pastucha, E., Nowaczyk, G., Mazurek, U., Plewka, D., Machnik, G., Wilczok, T., Colman, R.W. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  4. Association of the human bradykinin B2 receptor gene with chronic renal failure. Jozwiak, L., Drop, A., Buraczynska, K., Ksiazek, P., Mierzicki, P., Buraczynska, M. Mol. Diagn. (2004) [Pubmed]
  5. Identification of polymorphic sites of the human bradykinin B2 receptor gene. Braun, A., Kammerer, S., Böhme, E., Müller, B., Roscher, A.A. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  6. Bradykinin stimulates NF-kappaB activation and interleukin 1beta gene expression in cultured human fibroblasts. Pan, Z.K., Zuraw, B.L., Lung, C.C., Prossnitz, E.R., Browning, D.D., Ye, R.D. J. Clin. Invest. (1996) [Pubmed]
  7. Renal permeability alteration precedes hypertension and involves bradykinin in the spontaneously hypertensive rat. Plante, G.E., Bissonnette, M., Sirois, M.G., Regoli, D., Sirois, P. J. Clin. Invest. (1992) [Pubmed]
  8. Altered frequency of a promoter polymorphic allele of the kinin B1 receptor gene in inflammatory bowel disease. Bachvarov, D.R., Landry, M., Houle, S., Paré, P., Marceau, F. Gastroenterology (1998) [Pubmed]
  9. Regulation of nitric oxide production in human coronary microvessels and the contribution of local kinin formation. Kichuk, M.R., Seyedi, N., Zhang, X., Marboe, C.C., Michler, R.E., Addonizio, L.J., Kaley, G., Nasjletti, A., Hintze, T.H. Circulation (1996) [Pubmed]
  10. Delineation of a region in the B2 bradykinin receptor that is essential for high-affinity agonist binding. Nardone, J., Hogan, P.G. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  11. Identification of a B2-bradykinin receptor linked to phospholipase C and inhibition of dopamine stimulated cyclic AMP accumulation in the human astrocytoma cell line D384. Balmforth, A.J., Parkinson, F.E., Altiok, N., Fredholm, B.B. Naunyn Schmiedebergs Arch. Pharmacol. (1992) [Pubmed]
  12. The renal antifibrotic effects of angiotensin-converting enzyme inhibition involve bradykinin B2 receptor activation in angiotensin II-dependent hypertension. Seccia, T.M., Belloni, A.S., Guidolin, D., Sticchi, D., Nussdorfer, G.G., Pessina, A.C., Rossi, G.P. J. Hypertens. (2006) [Pubmed]
  13. Detrimental role of bradykinin B2 receptor in a murine model of diffuse brain injury. Hellal, F., Pruneau, D., Palmier, B., Faye, P., Croci, N., Plotkine, M., Marchand-Verrecchia, C. J. Neurotrauma (2003) [Pubmed]
  14. Inhibition of guinea pig skin allergic reactions by nonpeptide bradykinin B2 receptor antagonist FR173657. Mori, T., Imamura, T. Int. Arch. Allergy Immunol. (1998) [Pubmed]
  15. Expression cloning of a human B1 bradykinin receptor. Menke, J.G., Borkowski, J.A., Bierilo, K.K., MacNeil, T., Derrick, A.W., Schneck, K.A., Ransom, R.W., Strader, C.D., Linemeyer, D.L., Hess, J.F. J. Biol. Chem. (1994) [Pubmed]
  16. Characterization of two polymorphic sites in the human kinin B1 receptor gene: altered frequency of an allele in patients with a history of end-stage renal failure. Bachvarov, D.R., Landry, M., Pelletier, I., Chevrette, M., Betard, C., Houde, I., Bergeron, J., Lebel, M., Marceau, F. J. Am. Soc. Nephrol. (1998) [Pubmed]
  17. Spontaneous formation of a proteolytic B1 and B2 bradykinin receptor complex with enhanced signaling capacity. Kang, D.S., Ryberg, K., Mörgelin, M., Leeb-Lundberg, L.M. J. Biol. Chem. (2004) [Pubmed]
  18. Kinin B2 receptor-coupled signal transduction in human cultured keratinocytes. Vidal, M.A., Astroza, A., Matus, C.E., Ehrenfeld, P., Pavicic, F., Sanchez, T., Salem, C., Figueroa, J., Concha, M., Gonzalez, C.B., Figueroa, C.D. J. Invest. Dermatol. (2005) [Pubmed]
  19. Cloning and pharmacological characterization of a human bradykinin (BK-2) receptor. Hess, J.F., Borkowski, J.A., Young, G.S., Strader, C.D., Ransom, R.W. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  20. Structure and chromosomal localization of the gene (BDKRB2) encoding human bradykinin B2 receptor. Ma, J.X., Wang, D.Z., Ward, D.C., Chen, L., Dessai, T., Chao, J., Chao, L. Genomics (1994) [Pubmed]
  21. The human B1 bradykinin receptor exhibits high ligand-independent, constitutive activity. Roles of residues in the fourth intracellular and third transmembrane domains. Leeb-Lundberg, L.M., Kang, D.S., Lamb, M.E., Fathy, D.B. J. Biol. Chem. (2001) [Pubmed]
  22. Interaction of endothelial and neuronal nitric-oxide synthases with the bradykinin B2 receptor. Binding of an inhibitory peptide to the oxygenase domain blocks uncoupled NADPH oxidation. Golser, R., Gorren, A.C., Leber, A., Andrew, P., Habisch, H.J., Werner, E.R., Schmidt, K., Venema, R.C., Mayer, B. J. Biol. Chem. (2000) [Pubmed]
  23. Control of conformational equilibria in the human B2 bradykinin receptor. Modeling of nonpeptidic ligand action and comparison to the rhodopsin structure. Marie, J., Richard, E., Pruneau, D., Paquet, J.L., Siatka, C., Larguier, R., Poncé, C., Vassault, P., Groblewski, T., Maigret, B., Bonnafous, J.C. J. Biol. Chem. (2001) [Pubmed]
  24. Cellular localization of low-molecular-weight kininogen and bradykinin B2 receptor mRNAs in human kidney. Song, Q., Wang, D.Z., Harley, R.A., Chao, L., Chao, J. Am. J. Physiol. (1996) [Pubmed]
  25. Bradykinin upregulates IL-8 production in human gingival fibroblasts stimulated by interleukin-1beta and tumor necrosis factor alpha. Brunius, G., Domeij, H., Gustavsson, A., Yucel-Lindberg, T. Regul. Pept. (2005) [Pubmed]
  26. Ligand-induced phosphorylation/dephosphorylation of the endogenous bradykinin B2 receptor from human fibroblasts. Blaukat, A., Alla, S.A., Lohse, M.J., Müller-Esterl, W. J. Biol. Chem. (1996) [Pubmed]
  27. Modulation of bradykinin signaling by EP24.15 and EP24.16 in cultured trigeminal ganglia. Jeske, N.A., Berg, K.A., Cousins, J.C., Ferro, E.S., Clarke, W.P., Glucksman, M.J., Roberts, J.L. J. Neurochem. (2006) [Pubmed]
  28. Post-transcriptional regulation of bradykinin B1 and B2 receptor gene expression in human lung fibroblasts by tumor necrosis factor-alpha: modulation by dexamethasone. Haddad, E.B., Fox, A.J., Rousell, J., Burgess, G., McIntyre, P., Barnes, P.J., Chung, K.F. Mol. Pharmacol. (2000) [Pubmed]
  29. Activation of sphingosine kinase by the bradykinin B2 receptor and its implication in regulation of the ERK/MAP kinase pathway. Blaukat, A., Dikic, I. Biol. Chem. (2001) [Pubmed]
  30. Negative and positive regulatory epitopes in the C-terminal domains of the human B1 and B2 bradykinin receptor subtypes determine receptor coupling efficacy to G(q/11)-mediated [correction of G(9/11)-mediated] phospholipase Cbeta activity. Kang, D.S., Leeb-Lundberg, L.M. Mol. Pharmacol. (2002) [Pubmed]
  31. Expression and cellular localization of tissue kallikrein-kinin system in human adrenal gland. Wang, D.Z., Song, Q., Chen, L.M., Chao, L., Chao, J. Am. J. Physiol. (1996) [Pubmed]
  32. A novel protein-protein interaction between a G protein-coupled receptor and the phosphatase SHP-2 is involved in bradykinin-induced inhibition of cell proliferation. Duchene, J., Schanstra, J.P., Pecher, C., Pizard, A., Susini, C., Esteve, J.P., Bascands, J.L., Girolami, J.P. J. Biol. Chem. (2002) [Pubmed]
  33. Kinin B1 and B2 receptors are overexpressed in the hippocampus of humans with temporal lobe epilepsy. Perosa, S.R., Arga??araz, G.A., Goto, E.M., Costa, L.G., Konno, A.C., Varella, P.P., Santiago, J.F., Pesquero, J.B., Canzian, M., Amado, D., Yacubian, E.M., Carrete, H., Centeno, R.S., Cavalheiro, E.A., Silva, J.A., Mazzacoratti, M.d.a. .G. Hippocampus (2007) [Pubmed]
  34. Human B1 and B2 bradykinin receptors and their agonists target caveolae-related lipid rafts to different degrees in HEK293 cells. Lamb, M.E., Zhang, C., Shea, T., Kyle, D.J., Leeb-Lundberg, L.M. Biochemistry (2002) [Pubmed]
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