bradykinin receptors


Summary: Cell surface receptors that bind BRADYKININ and related KININS with high affinity and trigger intracellular changes which influence the behavior of cells. The identified receptor types (B-1 and B-2, or BK-1 and BK-2) recognize endogenous KALLIDIN; t-kinins; and certain bradykinin fragments as well as bradykinin itself.

Top Publications

  1. Noda M, Kariura Y, Amano T, Manago Y, Nishikawa K, Aoki S, et al. Expression and function of bradykinin receptors in microglia. Life Sci. 2003;72:1573-81 pubmed
    ..Our data provide the first evidence that microglia express functional BK receptors and support the idea that microglia play an important role in CNS inflammatory responses. ..
  2. Noda M, Kariura Y, Pannasch U, Nishikawa K, Wang L, Seike T, et al. Neuroprotective role of bradykinin because of the attenuation of pro-inflammatory cytokine release from activated microglia. J Neurochem. 2007;101:397-410 pubmed
    ..Our data imply that BK has anti-inflammatory and neuroprotective effects in the central nervous system by modulating microglial function. ..
  3. Luo M, Chen Q, Ossipov M, Rankin D, Porreca F, Lai J. Spinal dynorphin and bradykinin receptors maintain inflammatory hyperalgesia. J Pain. 2008;9:1096-105 pubmed publisher
    ..Recent findings implicate a direct excitatory action of dynorphin A at bradykinin receptors to promote hyperalgesia in nerve injured rats, and its upregulation may promote, rather than counteract, ..
  4. Lai J, Luo M, Chen Q, Ma S, Gardell L, Ossipov M, et al. Dynorphin A activates bradykinin receptors to maintain neuropathic pain. Nat Neurosci. 2006;9:1534-40 pubmed
    ..dynorphin induces calcium influx via voltage-sensitive calcium channels in sensory neurons by activating bradykinin receptors. This action of dynorphin at bradykinin receptors is distinct from the primary signaling pathway activated ..
  5. Hornig B, Kohler C, Schlink D, Tatge H, Drexler H. AT1-receptor antagonism improves endothelial function in coronary artery disease by a bradykinin/B2-receptor-dependent mechanism. Hypertension. 2003;41:1092-5 pubmed
    ..This effect is inhibited by either icatibant and or L-NMMA, suggesting that both bradykinin and NO contribute to the vascular effects of AT1-receptor antagonists in this patient population. ..
  6. Lamb M, Zhang C, Shea T, Kyle D, Leeb Lundberg L. Human B1 and B2 bradykinin receptors and their agonists target caveolae-related lipid rafts to different degrees in HEK293 cells. Biochemistry. 2002;41:14340-7 pubmed
    ..Our results show that B2R is constitutively targeted to CLR in HEK293 cells and appears to shuttle the agonist through these domains, whereas B1R may be there by default. ..
  7. Cruden N, Witherow F, Webb D, Fox K, Newby D. Bradykinin contributes to the systemic hemodynamic effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure. Arterioscler Thromb Vasc Biol. 2004;24:1043-8 pubmed
    ..This mechanism may explain the apparent clinical differences between ACE inhibitors and angiotensin receptor blockers in the treatment of heart failure. ..
  8. Witherow F, Helmy A, Webb D, Fox K, Newby D. Bradykinin contributes to the vasodilator effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure. Circulation. 2001;104:2177-81 pubmed
  9. Trendelenburg A, Meyer A, Klebroff W, Guimarães S, Starke K. Crosstalk between presynaptic angiotensin receptors, bradykinin receptors and alpha 2-autoreceptors in sympathetic neurons: a study in alpha 2-adrenoceptor-deficient mice. Br J Pharmacol. 2003;138:1389-402 pubmed
    ..The results hence also suggest that in addition to alpha(2A)- and alpha(2C)- mouse postganglionic sympathetic neurons possess alpha(2B)-autoreceptors. ..

More Information


  1. Lei Y, Zhang Y, Cao Y, Edvinsson L, Xu C. Up-regulation of bradykinin receptors in rat bronchi via I kappa B kinase-mediated inflammatory signaling pathway. Eur J Pharmacol. 2010;634:149-61 pubmed publisher
    ..intracellular signaling mechanisms may be involved in airway hyperresponsiveness through up-regulation of bradykinin receptors. This study was designed to examine if organ culture of rat bronchial segments induces airway ..
  2. Noda M, Kariura Y, Amano T, Manago Y, Nishikawa K, Aoki S, et al. Kinin receptors in cultured rat microglia. Neurochem Int. 2004;45:437-42 pubmed
    ..The presence of bradykinin receptors in microglia has been of great significance...
  3. Kuoppala A, Shiota N, Lindstedt K, Rysa J, Leskinen H, Luodonpää M, et al. Expression of bradykinin receptors in the left ventricles of rats with pressure overload hypertrophy and heart failure. J Hypertens. 2003;21:1729-36 pubmed
    ..However, ongoing pressure overload leads to a loss of BK-2Rs with a dramatic increase in left ventricular fibrosis followed by diastolic dysfunction and heart failure. ..
  4. Fox A, Wotherspoon G, McNair K, Hudson L, Patel S, Gentry C, et al. Regulation and function of spinal and peripheral neuronal B1 bradykinin receptors in inflammatory mechanical hyperalgesia. Pain. 2003;104:683-91 pubmed
    Activation of either B1 or B2 bradykinin receptors by kinins released from damaged tissues contributes to the development and maintenance of inflammatory hyperalgesia...
  5. Kuoppala A, Shiota N, Kokkonen J, Liesmaa I, Kostner K, Mayranpaa M, et al. Down-regulation of cardioprotective bradykinin type-2 receptors in the left ventricle of patients with end-stage heart failure. J Am Coll Cardiol. 2002;40:119-25 pubmed
    ..These results are the first to suggest that a loss of BK-2Rs is involved in the pathogenesis of human HF. ..
  6. Borkowski J, Ransom R, Seabrook G, Trumbauer M, Chen H, Hill R, et al. Targeted disruption of a B2 bradykinin receptor gene in mice eliminates bradykinin action in smooth muscle and neurons. J Biol Chem. 1995;270:13706-10 pubmed
    ..Therefore, expression of a single gene appears to be responsible for conferring responsiveness to bradykinin in these tissues. ..
  7. Ni A, Chai K, Chao L, Chao J. Molecular cloning and expression of rat bradykinin B1 receptor. Biochim Biophys Acta. 1998;1442:177-85 pubmed
    ..These results indicate that the cloned gene encodes a functional rat B1 receptor. ..
  8. Tschope C, Walther T, Yu M, Reinecke A, Koch M, Seligmann C, et al. Myocardial expression of rat bradykinin receptors and two tissue kallikrein genes in experimental diabetes. Immunopharmacology. 1999;44:35-42 pubmed
    ..This reduction is not compensated by elevated BK receptor levels. We suggest that alterations of the KKS may contribute to myocardial dysfunction in diabetes mellitus. ..
  9. Pesquero J, Pesquero J, Oliveira S, Roscher A, Metzger R, Ganten D, et al. Molecular cloning and functional characterization of a mouse bradykinin B1 receptor gene. Biochem Biophys Res Commun. 1996;220:219-25 pubmed
    ..This effect was not produced by bradykinin and could be blocked by the B1 antagonist des-Arg9Leu8BK. ..
  10. Vianna R, Calixto J. Characterization of the receptor and the mechanisms underlying the inflammatory response induced by des-Arg9-BK in mouse pleurisy. Br J Pharmacol. 1998;123:281-91 pubmed
  11. Katayama N, Iwata E, Sakurai H, Tsuchiya T, Tsuda M. Additive induction of Egr-1 (zif/268) mRNA expression in neuroblastoma x glioma hybrid NG108-15 cells via cholinergic muscarinic, alpha 2-adrenergic, and bradykinin receptors. J Neurochem. 1993;60:902-7 pubmed
    ..Thus, the signals transduced in NG108-15 cells by different neurotransmitter receptors appear to have different effects on Egr-1 induction, depending on the times of stimulation and the combinations of receptors stimulated. ..
  12. Griesbacher T, Rainer I. 5-hydroxytryptamine release from skin mast cells in vivo induced by peptide but not by nonpeptide ligands for bradykinin receptors. Immunopharmacology. 1999;43:195-201 pubmed
    ..It is concluded that the novel nonpeptide receptor ligands are devoid of the unspecific mast cell-degranulating action observed with the peptide ligands. ..
  13. Blaukat A, Alla S, Lohse M, Muller Esterl W. Ligand-induced phosphorylation/dephosphorylation of the endogenous bradykinin B2 receptor from human fibroblasts. J Biol Chem. 1996;271:32366-74 pubmed
    ..These finding point to a role of ligand-induced phosphorylation in the desensitization and redistribution of the bradykinin receptor in human fibroblasts. ..
  14. McLean P, Perretti M, Ahluwalia A. Inducible expression of the kinin B1 receptor in the endotoxemic heart: mechanisms of des-Arg9bradykinin-induced coronary vasodilation. Br J Pharmacol. 1999;128:275-82 pubmed
    ..Additionally, B1 receptor antagonists partially reversed endotoxin-induced hypotension. Therefore activation of B1 receptors may have a role to play in the vascular changes associated with endotoxemia. ..
  15. Tsukagoshi H, Horie T, Fukabori Y, Shimizu Y, Iwamae S, Hisada T, et al. Regulation by interleukin-1beta of gene expression of bradykinin B1 receptor in MH-S murine alveolar macrophage cell line. Biochem Biophys Res Commun. 1999;259:476-82 pubmed
    ..05 after a 100 nM des-Arg10-kallidin for 8 h), with an optimal effect at 3-100 nM. These data suggest that IL-1beta may up-regulate BDKRB1-mediated functions of alveolar macrophages via an induction of BDKRB1 gene expression. ..
  16. Kaplanski J, Asa I, Artru A, Azez A, Ivashkova Y, Rudich Z, et al. LF 16-0687 Ms, a new bradykinin B2 receptor antagonist, decreases ex vivo brain tissue prostaglandin E2 synthesis after closed head trauma in rats. Resuscitation. 2003;56:207-13 pubmed
    ..LF 16-0687 Ms also improved NSS and decreased brain water content by 51%. We conclude that the beneficial effect of LF 16-0687 Ms on outcome after CHT is accompanied by blockade of PGE(2) increase in injured brain tissue. ..
  17. Veeravalli K, Akula A, Kota M. Nitric oxide- and prostaglandin-mediated cardioprotection by bradykinin in myocardial ischemia and reperfusion injury. Pol J Pharmacol. 2003;55:1021-9 pubmed
  18. Ellis K, Fozard J. Species differences in bradykinin receptor-mediated responses of the airways. Auton Autacoid Pharmacol. 2002;22:3-16 pubmed
    ..5. Despite its many and varied effects in the airways of animals and man, the exact contribution of BK to airways disease remains unclear. ..
  19. Sabourin T, Bastien L, Bachvarov D, Marceau F. Agonist-induced translocation of the kinin B(1) receptor to caveolae-related rafts. Mol Pharmacol. 2002;61:546-53 pubmed
    ..Agonist-induced cellular translocation of the kinin B(1)R to caveolae-related rafts without endocytosis is a novel variation on the theme of G protein-coupled receptor adaptation. ..
  20. Gainer J, Brown N, Bachvarova M, Bastien L, Maltais I, Marceau F, et al. Altered frequency of a promoter polymorphism of the kinin B2 receptor gene in hypertensive African-Americans. Am J Hypertens. 2000;13:1268-73 pubmed
    ..75 v. 0.62, P = .009). Thus, this B2 receptor promoter polymorphism may represent a susceptibility marker for essential hypertension in African-Americans. ..
  21. Yan Feng W, Gang L, Yan Ting G. Bradykinin preconditioning induces protective effects on the spinal cord ischemic injury of rats. Neurosci Lett. 2008;433:114-8 pubmed publisher
  22. Cellier E, Duchene J, Pecher C, Alric C, Bascands J, Schanstra J, et al. B2 receptor activation reduces Erk1 and Erk2 phosphorylation induced by insulin-like growth factor-1, platelet-derived growth factor-BB, and high glucose in rat isolated glomeruli. Can J Physiol Pharmacol. 2002;80:341-5 pubmed
    ..These effects are consistent with the hypothesis of a protective role for BK in the kidney during development of glomerulosclerosis and renal pathologies associated with a hyperproliferative state. ..
  23. Blais C, LaPointe N, Rouleau J, Clement R, Gervais N, Geadah D, et al. Effects of the vasopeptidase inhibitor omapatrilat on cardiac endogenous kinins in rats with acute myocardial infarction. Peptides. 2001;22:953-62 pubmed
    ..Thus, the significant increase of cardiac BK concentrations by omapatrilat could be related to a biochemical or a cardiac hemodynamic parameter on early (24 h) post-MI state. ..
  24. Adam A, Blais C, Loute G. [Kinins: their nature and their potential role in the cardiovascular effects of angiotensin-converting enzyme inhibitors]. Nephrologie. 2000;21:163-72 pubmed
    ..This will allow to the nephrologist a better understanding of the role of these vasoactive peptides not only in the beneficial aspects, but also in the acute side-effects, of angiotensin-converting enzyme inhibitors. ..
  25. Noda M, Sasaki K, Ifuku M, Wada K. Multifunctional effects of bradykinin on glial cells in relation to potential anti-inflammatory effects. Neurochem Int. 2007;51:185-91 pubmed
    ..These observations may help to understand the paradox on the role of kinins in the central nervous system and may be useful for therapeutic strategy. ..
  26. Fukuo K, Yang J, Yasuda O, Mogi M, Suhara T, Sato N, et al. Nifedipine indirectly upregulates superoxide dismutase expression in endothelial cells via vascular smooth muscle cell-dependent pathways. Circulation. 2002;106:356-61 pubmed
    ..This finding may provide further insight into the mechanism underlying the beneficial effects of calcium antagonists in cardiovascular diseases. ..
  27. Li Y, Sato T. Dual signaling via protein kinase C and phosphatidylinositol 3'-kinase/Akt contributes to bradykinin B2 receptor-induced cardioprotection in guinea pig hearts. J Mol Cell Cardiol. 2001;33:2047-53 pubmed
    ..9+/-2.9%). We conclude that BK B2 receptors can precondition guinea pig hearts via the dual activation of PKC and PI3-K. The mitoK(ATP) channels act as downstream targets of PKC, whereas PI3-K is not associated with mitoK(ATP) channels. ..
  28. Chan D, Gera L, Stewart J, Helfrich B, Zhao T, Feng W, et al. Bradykinin antagonist dimer, CU201, inhibits the growth of human lung cancer cell lines in vitro and in vivo and produces synergistic growth inhibition in combination with other antitumor agents. Clin Cancer Res. 2002;8:1280-7 pubmed
    ..These studies are in progress through the NCI RAID mechanism. ..
  29. Paegelow I, Trzeczak S, Böckmann S, Vietinghoff G. Migratory responses of polymorphonuclear leukocytes to kinin peptides. Pharmacology. 2002;66:153-61 pubmed
  30. Böckmann S, Paegelow I. Kinins and kinin receptors: importance for the activation of leukocytes. J Leukoc Biol. 2000;68:587-92 pubmed
    ..An upregulation of kinin receptors on neutrophils and macrophages appears to be involved in increasing the sensitivity of these cells to kinins at the site of inflammation. ..
  31. Brechter A, Lerner U. Characterization of bradykinin receptors in a human osteoblastic cell line. Regul Pept. 2002;103:39-51 pubmed
  32. Sot U, Misterek K, Gumułka S, Dorociak A. Intrathecal bradykinin administration: opposite effects on nociceptive transmission. Pharmacology. 2002;66:76-80 pubmed
    ..The results obtained in this study showed that--depending on the dose used--BK and des-Arg(9)-BK could produce pro- as well as antinociceptive actions. Both B(2) and B(1) receptors are involved in the action of intrathecally applied BK. ..
  33. Meini S, Bellucci F, Cucchi P, Giuliani S, Quartara L, Giolitti A, et al. Bradykinin B2 and GPR100 receptors: a paradigm for receptor signal transduction pharmacology. Br J Pharmacol. 2004;143:938-41 pubmed
  34. Huang C, Tliba O, Panettieri R, Amrani Y. Bradykinin induces interleukin-6 production in human airway smooth muscle cells: modulation by Th2 cytokines and dexamethasone. Am J Respir Cell Mol Biol. 2003;28:330-8 pubmed
    ..Moreover, IL-6 secretion by BK is sensitive to corticosteroids and is regulated by Th(2)-derived cytokines. ..
  35. Gabra B, Sirois P. Role of bradykinin B(1) receptors in diabetes-induced hyperalgesia in streptozotocin-treated mice. Eur J Pharmacol. 2002;457:115-24 pubmed
  36. Koba S, Xing J, Sinoway L, Li J. Bradykinin receptor blockade reduces sympathetic nerve response to muscle contraction in rats with ischemic heart failure. Am J Physiol Heart Circ Physiol. 2010;298:H1438-44 pubmed publisher
    ..These data suggest that bradykinin within contracting muscle is part of the exaggerated muscle reflex seen in CHF. ..
  37. Uknis A, Dela Cadena R, Janardham R, Sartor R, Whalley E, Colman R. Bradykinin receptor antagonists type 2 attenuate the inflammatory changes in peptidoglycan-induced acute arthritis in the Lewis rat. Inflamm Res. 2001;50:149-55 pubmed
    ..These results indicate that the systemic inflammation is due in part to BK generation which can be blocked by B2-RA, while inhibiting the B1 receptor prevents an anti-inflammatory response. ..
  38. Wille P, Vitor R, Gabilan N, Nicolau M. Plasma extravasation mediated by lipopolysaccharide-induction of kinin B1 receptors in rat tissues. Mediators Inflamm. 2001;10:163-7 pubmed
  39. Leeb Lundberg L, Marceau F, Muller Esterl W, Pettibone D, Zuraw B. International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev. 2005;57:27-77 pubmed
    ..This review is a comprehensive presentation of our current understanding of these receptors in terms of molecular and cell biology, physiology, pharmacology, and involvement in human disease and drug development. ..
  40. Plendl J, Snyman C, Bhoola K. Visualization of the sequential changes in immunolabelled tissue kininogenase which accompany follicular development and luteinization of angiogenic granulosa cells of the ovary. Int Immunopharmacol. 2002;2:1981-94 pubmed
  41. Zausinger S. Bradykinin receptor antagonists in cerebral ischemia and trauma. IDrugs. 2003;6:970-5 pubmed
    ..Accordingly, specific inhibition of bradykinin B2 receptors attenuates brain swelling and limits tissue damage, indicating its potential in patients with acute cerebral ischemia and trauma. ..
  42. Meini S, Lecci A, Carini F, Tramontana M, Giuliani S, Maggi C, et al. In vitro and in vivo activity of analogues of the kinin B2 receptor antagonist MEN1 1270. Can J Physiol Pharmacol. 2002;80:293-302 pubmed
  43. Eric J, Gabra B, Sirois P. Implication of the bradykinin receptors in antigen-induced pulmonary inflammation in mice. Br J Pharmacol. 2003;138:1589-97 pubmed
    ..Such effects were inhibited by HOE-140 (10 microg kg(-1)). 5. Our results suggest that the airway inflammatory response induced by antigen challenge in mice is mediated by stimulation of both BKB(1)-R and BKB(2)-R. ..
  44. Bachvarov D, Houle S, Bachvarova M, Bouthillier J, Adam A, Marceau F. Bradykinin B(2) receptor endocytosis, recycling, and down-regulation assessed using green fluorescent protein conjugates. J Pharmacol Exp Ther. 2001;297:19-26 pubmed
    ..Digestion initiated by extracellular proteases may be involved in pathological B2R down-regulation, as suggested by the simulation involving trypsin. ..
  45. Blaukat A, Micke P, Kalatskaya I, Faussner A, Muller Esterl W. Downregulation of bradykinin B2 receptor in human fibroblasts during prolonged agonist exposure. Am J Physiol Heart Circ Physiol. 2003;284:H1909-16 pubmed
    ..e., by attenuation of de novo synthesis and by reduction of receptor stability. ..
  46. Zhang S, Wang H, Lovenberg T, Codd E. Functional studies of bradykinin receptors in Chinese hamster ovary cells stably expressing the human B2 bradykinin receptor. Int Immunopharmacol. 2001;1:955-65 pubmed
    ..kallidin > DALKD > [des-Arg10] kallidin (DAKD), consistent with the pharmacological profile of B2 bradykinin receptors. The B2 agonist bradykinin and the B1/B2 agonist kallidin, but not the B1 agonist DAKD, increased [35S]GTP ..
  47. Kunapuli P, Ransom R, Murphy K, Pettibone D, Kerby J, Grimwood S, et al. Development of an intact cell reporter gene beta-lactamase assay for G protein-coupled receptors for high-throughput screening. Anal Biochem. 2003;314:16-29 pubmed
    ..The beta-lactamase assay has been optimized for cell density, time of agonist stimulation, and DMSO sensitivity. This CHO-hBK1-beta-lactamase assay is well suited to automation and miniaturization required for high-throughput screening. ..
  48. Camarda V, Rizzi A, Calo G, Wirth K, Regoli D. Pharmacological characterisation of novel kinin B2 receptor ligands. Can J Physiol Pharmacol. 2002;80:281-6 pubmed
    ..9) than in rabbit (7.6) and pig (9.4). Two other compounds (FR 173657 and FR 172357) show similar pharmacological spectra as S 1567 and differ from LF 160687. ..
  49. Yu J, Prado G, Taylor L, Piserchio A, Gupta A, Mierke D, et al. Global chimeric exchanges within the intracellular face of the bradykinin B2 receptor with corresponding angiotensin II type Ia receptor regions: generation of fully functional hybrids showing characteristic signaling of the AT1a receptor. J Cell Biochem. 2002;85:809-19 pubmed
  50. Sawant S, Snyman C, Bhoola K. Comparison of tissue kallikrein and kinin receptor expression in gastric ulcers and neoplasms. Int Immunopharmacol. 2001;1:2063-80 pubmed
    ..This is a first study that provides strong evidence for enhanced expression of TK in peptic ulceration and gastric malignancy, suggestive of a crucial role for serine proteases in cancer. ..
  51. Emerich D, Snodgrass P, Dean R, Lafreniere D, Agostino M, Wiens T, et al. Bradykinin modulation of tumor vasculature: I. Activation of B2 receptors increases delivery of chemotherapeutic agents into solid peripheral tumors, enhancing their efficacy. J Pharmacol Exp Ther. 2001;296:623-31 pubmed
  52. Lavich T, Cordeiro R, Calixto J, E Silva P, Martins M. Combined action of vasoactive amines and bradykinin mediates allergen-evoked thermal hyperalgesia in rats. Eur J Pharmacol. 2003;462:185-92 pubmed
    ..Our findings show that local thermal hyperalgesia is a feature of allergen-evoked inflammation, and that a synergistic interaction among bradykinin, 5-hydroxytryptamine and histamine plays a critical role in this phenomenon. ..
  53. Harrison Bernard L, Dipp S, El Dahr S. Renal and blood pressure phenotype in 18-mo-old bradykinin B2R(-/-)CRD mice. Am J Physiol Regul Integr Comp Physiol. 2003;285:R782-90 pubmed
    ..This novel model of human disease links gene-environment interactions with renal development and blood pressure homeostasis. ..