Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Bradykinin Receptors

  • Vicência SalesEmail author
  • João Bosco Pesquero
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_232


 B1BKR;  B1R;  B2BKR;  B2R;  BDKRB1;  BDKRB2;  BKB1R;  BKB2R;  BKR1;  BKR2;  Kinin B1;  Kinin B2

Historical Background

A primary mediator of inflammation, the nonapeptide bradykinin (BK) is a pharmacologically active peptide of the kinin group released in tissues and circulation as a consequence of coagulation cascade activation, more specifically by the kininogen cleavage by kallikrein. The enzyme kallikrein was described in 1930 by Werle and Frey. It was the first component of the kallikrein-kinin system (KKS) discovered, followed by the identification of bradykinin (BK) by Rocha e Silva and colleagues in 1949. In 1970s Regoli and coworkers characterized molecularly the two subtypes of kinin receptors B 1 and B 2, based in their pharmacological and expression profiles differences (Fig. 1). These findings enabled the subsequent development of different agonists and antagonists for these receptors (Leeb-Lundberg et al. 2005). The genes encoding these receptors were cloned in...
This is a preview of subscription content, log in to check access.


  1. Borkowski JA, Ransom RW, Seabrook GR, Trumbauer M, Chen H, Hill RG, Strader CD, Hess JF. Targeted disruption of a B2 bradykinin receptor gene in mice eliminates bradykinin action in smooth muscle and neurons. J Biol Chem. 1995;270(23):13706–10.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Brechter AB, Persson E, Lundgren I, Lerner UH. Kinin B1 and B2 receptor expression in osteoblasts and fibroblasts is enhanced by interleukin-1 and tumour necrosis factor-alpha. Effects dependent on activation of NF-kappaB and MAP kinases. Bone. 2008;43(1):72–83.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Cayla C, Merino VF, Cabrini DA, Silva Jr JA, Pesquero JB, Bader M. Structure of the mammalian kinin receptor gene locus. Int Immunopharmacol. 2002;2(13–14):1721–7. (Review).PubMedPubMedCentralCrossRefGoogle Scholar
  4. Cayla C, Todiras M, Iliescu R, et al. Mice deficient for both kinin receptors are normotensive and protected from endotoxin-induced hypotension. FASEB J. 2007;21(8):1689–98.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Couture R, Harrisson M, Vianna RM, Cloutier F. Kinin receptors in pain and inflammation. Eur J Pharmacol. 2001;429(1–3):161–76. (Review).PubMedPubMedCentralCrossRefGoogle Scholar
  6. Damas J, Garbacki N, Lefèbvre PJ. The kallikrein-kinin system, angiotensin converting enzyme inhibitors and insulin sensitivity. Diabetes Metab Res Rev. 2004;20(4):288–97. (Review).PubMedPubMedCentralCrossRefGoogle Scholar
  7. Kakoki M, Kizer CM, Yi X, Takahashi N, Kim HS, Bagnell CR, Edgell CJ, Maeda N, Jennette JC, Smithies O. Senescence-associated phenotypes in Akita diabetic mice are enhanced by absence of bradykinin B2 receptors. J Clin Invest. 2006;116(5):1302–9.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Kakoki M, Sullivan KA, Backus C, Hayes JM, SS O, Hua K, Gasim AM, Tomita H, Grant R, Nossov SB, Kim HS, Jennette JC, Feldman EL, Smithies O. Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice. Proc Natl Acad Sci U S A. 2010;107(22):10190–5.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Klein J, Gonzalez J, Decramer S, Bandin F, Neau E, Salant DJ, Heeringa P, Pesquero JB, Schanstra JP, Bascands JL. Blockade of the kinin B1 receptor ameloriates glomerulonephritis. J Am Soc Nephrol. 2010;21(7):1157–64.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Kouyoumdjian M, Nagaoka MR, Borges DR. Kallikrein-kinin system in hepatic experimental models. Peptides. 2005;26(8):1301–7. (Epub 26 Apr 2005. Review).PubMedPubMedCentralCrossRefGoogle Scholar
  11. Leeb-Lundberg LM, Marceau F, Müller-Esterl W, Pettibone DJ, Zuraw BL. International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev. 2005;57(1):27–77. (Review).PubMedPubMedCentralCrossRefGoogle Scholar
  12. Lemos MT, Amaral FA, Dong KE, Bittencourt MF, Caetano AL, Pesquero JB, Viel TA, Buck HS. Role of kinin B1 and B2 receptors in memory consolidation during the aging process of mice. Neuropeptides. 2010;44(2):163–8.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Merino VF, Todiras M, Mori MA, Sales VM, Fonseca RG, Saul V, Tenner K, Bader M, Pesquero JB. Predisposition to atherosclerosis and aortic aneurysms in mice deficient in kinin B1 receptor and apolipoprotein E. J Mol Med. 2009;87(10):953–63.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Mori MA, Araújo RC, Reis FC, Sgai DG, Fonseca RG, Barros CC, Merino VF, Passadore M, Barbosa AM, Ferrari B, Carayon P, Castro CH, Shimuta SI, Luz J, Bascands JL, Schanstra JP, Even PC, Oliveira SM, Bader M, Pesquero JB. Kinin B1 receptor deficiency leads to leptin hypersensitivity and resistance to obesity. Diabetes. 2008;57(6):1491–500.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Pesquero JB, Araujo RC, Heppenstall PA, Stucky CL, Silva Jr JA, Walther T, Oliveira SM, Pesquero JL, Paiva AC, Calixto JB, Lewin GR, Bader M. Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors. Proc Natl Acad Sci U S A. 2000;97(14):8140–5.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Proud D. The kinin system in rhinitis and asthma. Clin Rev Allergy Immunol. 1998;16(4):351–64. (Review).PubMedPubMedCentralCrossRefGoogle Scholar
  17. Sabatini RA, Guimarães PB, Fernandes L, Reis FC, Bersanetti PA, Mori MA, Navarro A, Hilzendeger AM, Santos EL, Andrade MC, Chagas JR, Pesquero JL, Casarini DE, Bader M, Carmona AK, Pesquero JB. ACE activity is modulated by kinin B2 receptor. Hypertension. 2008;51(3):689–95.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Schulze-Topphoff U, Prat A, Bader M, Zipp F, Aktas O. Roles of the kallikrein/kinin system in the adaptive immune system. Int Immunopharmacol. 2008;8(2):155–60. (Epub 22 Aug 2007. Review).PubMedPubMedCentralCrossRefGoogle Scholar
  19. Schulze-Topphoff U, Prat A, Prozorovski T, Siffrin V, Paterka M, Herz J, Bendix I, Ifergan I, Schadock I, Mori MA, Van Horssen J, Schröter F, Smorodchenko A, Han MH, Bader M, Steinman L, Aktas O, Zipp F. Activation of kinin receptor B1 limits encephalitogenic T lymphocyte recruitment to the central nervous system. Nat Med. 2009;15(7):788–93.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Sharma JN. Does the kinin system mediate in cardiovascular abnormalities? Na overview. J Clin Pharmacol. 2003;43(11):1187–95. (Review).PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Biophysics DepartmentUniversidade Federal de São PauloSão PauloBrazil