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Gene Review

Bdkrb2  -  bradykinin receptor B2

Rattus norvegicus

Synonyms: B2 bradykinin receptor, B2BKR, B2BRA, B2R, BK-2 receptor
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Disease relevance of Bdkrb2


Psychiatry related information on Bdkrb2

  • The two analogues alone and the fragment BK-(1-8), a potent stimulant of B1-receptors for BK, failed to alter reaction time and only the B2-receptor antagonist reduced BK-induced behavioural responses [5].

High impact information on Bdkrb2

  • Two months after MI, rats were treated for 2 mo with: (a) vehicle; (b) the ACEi ramipril, with and without the B2 receptor antagonist icatibant (B2-ant); or (c) an AT1-ant with and without an AT2-antagonist (AT2-ant) or B2-ant [6].
  • MBP and poly-L-lysine induced an increase in airway responsiveness, which was inhibited by pretreatment with a selective BK-2 receptor antagonist, NPC 17713 (250 micrograms/ml) [7].
  • [Thi5,8,DPhe7]bradykinin, where Thi is beta-(2-thienyl)-alanine, is a very weak partial agonist and inhibits the bradykinin-mediated ion flux, suggesting the cDNA encodes a smooth muscle, rather than a neuronal, B2 receptor subtype [8].
  • In competitive binding assays, unlabeled BK, Hoe 140 (a specific BK B2 receptor antagonist), and des-Arg9,[Leu8]BK (a BK B1 receptor antagonist) displaced [125I-Tyr8]BK with an IC50 of 4.3, 0.041, and 307 nmol/L, respectively [9].
  • Homodimers of an amino-terminal extended BK analog and a V1a-selective antagonist represent the first examples of new classes of B2 BKR and V1a VPR antagonists, respectively [10].

Chemical compound and disease context of Bdkrb2


Biological context of Bdkrb2


Anatomical context of Bdkrb2


Associations of Bdkrb2 with chemical compounds

  • In contrast, B2 receptor blockade had no effect or even increased these angiotensin II effects [16].
  • Only combined administration of B1R and B2R antagonists produced a significant BP increase from a baseline of 107-119 mmHg at end point, which could be partly prevented by losartan and was not associated with change in catecholamines, suggesting no involvement of the sympathoadrenal system [17].
  • The biochemical properties of the solubilised B2 BK receptor correspond to those of a hydrophobic acidic glycoprotein (isoelectric focusing gave a value of 4.5-4.7) that binds specifically to wheat germ agglutinin but has no affinity for either concanavalin A or lentil lectin, suggesting the absence of terminal mannose or glucose residues [25].
  • The B2 bradykinin receptor antagonist HOE 140 and the B1 bradykinin receptor antagonist des-Arg9[Leu8]bradykinin displaced the binding of [3H]bradykinin from dog membranes with IC50 values of 0.38 and 217.3 nmol/l, respectively, suggesting that bradykinin binds to a B2-type receptor [26].
  • In competitive experiments using membranes prepared from Chinese hamster ovary cells expressing the human bradykinin receptor subtypes, FR190997 showed a high affinity binding to the B2 receptor with IC50 value of 5.3 nM and no binding affinity for the B1 receptor [27].

Regulatory relationships of Bdkrb2

  • Superfusion with Bk (10 nM) increased [Ca++]i by 96 +/- 10 nM over basal levels in approximately 80% of the neurons tested that were not affected by a Bk-1 receptor antagonist but were inhibited 72% by a Bk-2 receptor antagonist [28].
  • We investigated whether endogenous kinin levels are subject to short-loop-feedback regulation mediated by the B2 receptor and whether endogenous kinins acting through the B2 receptor influence plasma renin levels and circulating and tissue angiotensin peptide levels [29].
  • The B2 receptor antagonists had no significant inhibitory effects on kallidin-stimulated phosphoinositide metabolism or prolactin release [30].

Other interactions of Bdkrb2

  • Our findings indicate that the bradykinin 2 receptor (B2R) but not the bradykinin 1 receptor (B1R) is expressed in control bladder urothelium [21].
  • Synovitis-enhanced endothelial cell proliferation was also inhibited by the B2 receptor antagonist alone (27%) but not by the NK1 receptor antagonist alone [23].
  • The nonselective cyclooxygenase (COX) inhibitors S-(-)-ketoprofen (10 microM) and piroxicam (30 microM) markedly depressed the concentration-response curves to [desArg9]-BK and [Hyp3, Tyr(Me)8]-BK in control bladders, but neither drug affected the B1 or B2 receptor agonist-mediated responses in inflamed bladders [31].
  • HOE 140, a BK2 receptor antagonist (0.01, 0.1, and 1 nmol/L), prevented the stimulatory effect of BK on glucagon secretion in a concentration-dependent manner [32].
  • CONCLUSIONS: A new inhibitory pathway of the early steps of IGF-I signaling by the B2 receptor is found both in cultured MCs and in IG, which involves a calcium-dependent tyrosine phosphatase activity [33].

Analytical, diagnostic and therapeutic context of Bdkrb2


  1. Regulation of cardiac bradykinin B1- and B2-receptor mRNA in experimental ischemic, diabetic, and pressure-overload-induced cardiomyopathy. Spillmann, F., Altmann, C., Scheeler, M., Barbosa, M., Westermann, D., Schultheiss, H.P., Walther, T., Tschöpe, C. Int. Immunopharmacol. (2002) [Pubmed]
  2. Role of bradykinin B2 receptors in the formation of vasogenic brain edema in rats. Plesnila, N., Schulz, J., Stoffel, M., Eriskat, J., Pruneau, D., Baethmann, A. J. Neurotrauma (2001) [Pubmed]
  3. Down-regulation of bradykinin B2-receptor mRNA in the heart in pressure-overload cardiac hypertrophy in the rat. Yayama, K., Matsuoka, S., Nagaoka, M., Shimazu, E., Takano, M., Okamoto, H. Biochem. Pharmacol. (2003) [Pubmed]
  4. Therapeutical efficacy of a novel non-peptide bradykinin B2 receptor antagonist on brain edema formation and ischemic tissue damage in focal cerebral ischemia. Zausinger, S., Lumenta, D.B., Pruneau, D., Schmid-Elsaesser, R., Plesnila, N., Baethmann, A. Acta Neurochir. Suppl. (2003) [Pubmed]
  5. Bradykinin analogue blocks bradykinin-induced inhibition of a spinal nociceptive reflex in the rat. Laneuville, O., Couture, R. Eur. J. Pharmacol. (1987) [Pubmed]
  6. Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors. Liu, Y.H., Yang, X.P., Sharov, V.G., Nass, O., Sabbah, H.N., Peterson, E., Carretero, O.A. J. Clin. Invest. (1997) [Pubmed]
  7. Human eosinophil-granule major basic protein and synthetic polycations induce airway hyperresponsiveness in vivo dependent on bradykinin generation. Coyle, A.J., Ackerman, S.J., Burch, R., Proud, D., Irvin, C.G. J. Clin. Invest. (1995) [Pubmed]
  8. Expression cloning of a rat B2 bradykinin receptor. McEachern, A.E., Shelton, E.R., Bhakta, S., Obernolte, R., Bach, C., Zuppan, P., Fujisaki, J., Aldrich, R.W., Jarnagin, K. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  9. Characterization of bradykinin B2 receptors in adult myocardium and neonatal rat cardiomyocytes. Minshall, R.D., Nakamura, F., Becker, R.P., Rabito, S.F. Circ. Res. (1995) [Pubmed]
  10. Chimeric strategies for the rational design of bioactive analogs of small peptide hormones. Howl, J., Langel, U., Hawtin, S.R., Valkna, A., Yarwood, N.J., Saar, K., Wheatley, M. FASEB J. (1997) [Pubmed]
  11. Hyperalgesia in rats following intracerebroventricular administration of endotoxin: effect of bradykinin B1 and B2 receptor antagonist treatment. Walker, K., Dray, A., Perkins, M. Pain (1996) [Pubmed]
  12. Central involvement of kinin B1 and B2 receptors in the febrile response induced by endotoxin in rats. Coelho, M.M., Oliveira, C.R., Pajolla, G.P., Calixto, J.B., Pelá, I.R. Br. J. Pharmacol. (1997) [Pubmed]
  13. Kinin B2 receptor is not involved in enalapril-induced apoptosis and regression of hypertrophy in spontaneously hypertensive rat aorta: possible role of B1 receptor. Duguay, D., Der Sarkissian, S., Kouz, R., Ongali, B., Couture, R., deBlois, D. Br. J. Pharmacol. (2004) [Pubmed]
  14. Inflammatory hyperalgesia induced by zymosan in the plantar tissue of the rat: effect of kinin receptor antagonists. Bélichard, P., Landry, M., Faye, P., Bachvarov, D.R., Bouthillier, J., Pruneau, D., Marceau, F. Immunopharmacology (2000) [Pubmed]
  15. Effects of ACE inhibition and bradykinin antagonism on cardiovascular changes in uremic rats. Amann, K., Gassmann, P., Buzello, M., Orth, S.R., Törnig, J., Gross, M.L., Magener, A., Mall, G., Ritz, E. Kidney Int. (2000) [Pubmed]
  16. Contribution of bradykinin and nitric oxide to AT2 receptor-mediated differentiation in PC12 W cells. Zhao, Y., Biermann, T., Luther, C., Unger, T., Culman, J., Gohlke, P. J. Neurochem. (2003) [Pubmed]
  17. Role of bradykinin B1 and B2 receptors in normal blood pressure regulation. Duka, A., Duka, I., Gao, G., Shenouda, S., Gavras, I., Gavras, H. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  18. Induction of B1 receptors in streptozotocin diabetic rats: possible involvement in the control of hyperglycemia-induced glomerular Erk 1 and 2 phosphorylation. Mage, M., Pécher, C., Neau, E., Cellier, E., Dos Reiss, M.L., Schanstra, J.P., Couture, R., Bascands, J.L., Girolami, J.P. Can. J. Physiol. Pharmacol. (2002) [Pubmed]
  19. Two functionally divergent p53-responsive elements in the rat bradykinin B2 receptor promoter. Marks, J., Saifudeen, Z., Dipp, S., El-Dahr, S.S. J. Biol. Chem. (2003) [Pubmed]
  20. Molecular structure and expression of rat bradykinin B2 receptor gene. Evidence for alternative splicing. Pesquero, J.B., Lindsey, C.J., Zeh, K., Paiva, A.C., Ganten, D., Bader, M. J. Biol. Chem. (1994) [Pubmed]
  21. Expression and function of bradykinin B1 and B2 receptors in normal and inflamed rat urinary bladder urothelium. Chopra, B., Barrick, S.R., Meyers, S., Beckel, J.M., Zeidel, M.L., Ford, A.P., de Groat, W.C., Birder, L.A. J. Physiol. (Lond.) (2005) [Pubmed]
  22. B2 bradykinin receptor mediates the stimulatory effect of bradykinin on rat germ cell proliferation in vitro. Atanassova, N.N. Andrologia (2003) [Pubmed]
  23. Combined effect of bradykinin B2 and neurokinin-1 receptor activation on endothelial cell proliferation in acute synovitis. Seegers, H.C., Avery, P.S., McWilliams, D.F., Haywood, L., Walsh, D.A. FASEB J. (2004) [Pubmed]
  24. Interactions between bradykinin (BK) and cell adhesion molecule (CAM) expression in peptidoglycan-polysaccharide (PG-PS)-induced arthritis. Sainz, I.M., Uknis, A.B., Isordia-Salas, I., Dela Cadena, R.A., Pixley, R.A., Colman, R.W. FASEB J. (2004) [Pubmed]
  25. Purification and characterisation of B2 bradykinin receptor from rat uterus. Yaqoob, M., Snell, C.R. J. Neurochem. (1994) [Pubmed]
  26. Bradykinin B2 receptors on skeletal muscle are coupled to inositol 1,4,5-trisphosphate formation. Rabito, S.F., Minshall, R.D., Nakamura, F., Wang, L.X. Diabetes (1996) [Pubmed]
  27. Nonpeptide mimic of bradykinin with long-acting properties at the bradykinin B2 receptor. Aramori, I., Zenkoh, J., Morikawa, N., Asano, M., Hatori, C., Sawai, H., Kayakiri, H., Satoh, S., Inoue, T., Abe, Y., Sawada, Y., Mizutani, T., Inamura, N., Nakahara, K., Kojo, H., Oku, T., Notsu, Y. Mol. Pharmacol. (1997) [Pubmed]
  28. Bradykinin (Bk) increases cytosolic calcium in cultured rat myenteric neurons via Bk-2 type receptors coupled to mobilization of extracellular and intracellular sources of calcium: evidence that calcium influx is prostaglandin dependent. Gelperin, D., Mann, D., del Valle, J., Wiley, J.W. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  29. Type 2 bradykinin-receptor antagonism does not modify kinin or angiotensin peptide levels. Campbell, D.J., Kladis, A., Briscoe, T.A., Zhuo, J. Hypertension (1999) [Pubmed]
  30. Kallidin-induced stimulation of inositol phosphate production and prolactin release in rat anterior pituitary cells. Jones, T.H., Brown, B.L., Dobson, P.R. Acta Endocrinol. (1990) [Pubmed]
  31. Inflammation modifies the role of cyclooxygenases in the contractile responses of the rat detrusor smooth muscle to kinin agonists. Meini, S., Lecci, A., Cucchi, P., Catalioto, R.M., Criscuoli, M., Maggi, C.A. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  32. Stimulatory effect of bradykinin (BK) on glucagon secretion from the perfused rat pancreas: involvement of BK2 receptors. Abu-Basha, E.A., Makowski, J.P., Yibchok-anun, S., Hsu, W.H. Metab. Clin. Exp. (2000) [Pubmed]
  33. Inhibition of IGF-I-induced Erk 1 and 2 activation and mitogenesis in mesangial cells by bradykinin. Alric, C., Pecher, C., Cellier, E., Schanstra, J.P., Poirier, B., Chevalier, J., Bascands, J.L., Girolami, J.P. Kidney Int. (2002) [Pubmed]
  34. Age-related changes of bradykinin B1 and B2 receptors in rat heart. Kintsurashvili, E., Duka, A., Ignjacev, I., Pattakos, G., Gavras, I., Gavras, H. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  35. Tissue kallikrein and bradykinin B2 receptors in the reproductive tract of the male rat. Monsees, T.K., Blöcher, S., Loddo, C., Steger, K., Schill, W.B. Andrologia (2003) [Pubmed]
  36. Molecular cloning and sequence analysis of rat bradykinin B2 receptor gene. Wang, D.Z., Ma, J.X., Chao, L., Chao, J. Biochim. Biophys. Acta (1994) [Pubmed]
  37. Early activation of bradykinin B2 receptor aggravates reactive oxygen species generation and renal damage in ischemia/reperfusion injury. Chiang, W.C., Chien, C.T., Lin, W.W., Lin, S.L., Chen, Y.M., Lai, C.F., Wu, K.D., Chao, J., Tsai, T.J. Free Radic. Biol. Med. (2006) [Pubmed]
  38. Differential induction of functional B1-bradykinin receptors along the rat nephron in endotoxin induced inflammation. Marin-Castaño, M.E., Schanstra, J.P., Praddaude, F., Pesquero, J.B., Ader, J.L., Girolami, J.P., Bascands, J.L. Kidney Int. (1998) [Pubmed]
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