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Bradykinin receptors C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
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Bradykinin (or kinin) receptors (nomenclature as agreed by the NC-IUPHAR subcommittee on Bradykinin (kinin) Receptors [15]) are activated by the endogenous peptides bradykinin (KNG1, P01042) (BK), [des-Arg9]bradykinin (KNG1, P01042), Lys-BK (kallidin (KNG1, P01042)), [des-Arg10]kallidin (KNG1, P01042), [Phospho-Ser6]-Bradykinin, T-kinin (KNG1, P01042) (Ile-Ser-BK), [Hyp3]bradykinin (KNG1, P01042) and Lys-[Hyp3]-bradykinin (KNG1, P01042). Variation in pharmacology and activity of B1 and B2 receptor antagonists at species orthologs has been documented. Icatibant (Hoe140, Firazir) is approved in North America and Europe for the treatment of acute attacks of hereditary angioedema. Inhibition of bradykinin with icatibant in COVID-19 infection is under clinical evaluation, with trial NCT05407597 expected to complete in mid 2023.
Receptors
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B1 receptor
C
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B2 receptor
C
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Further reading
* Key recommended reading is highlighted with an asterisk
* Blaes N, Girolami JP. (2013) Targeting the 'Janus face' of the B2-bradykinin receptor. Expert Opin Ther Targets, 17 (10): 1145-66. [PMID:23957374]
* Brusco I, Fialho MFP, Becker G, Brum ES, Favarin A, Marquezin LP, Serafini PT, Oliveira SM. (2023) Kinins and their B1 and B2 receptors as potential therapeutic targets for pain relief. Life Sci, 314: 121302. [PMID:36535404]
Calixto JB, Medeiros R, Fernandes ES, Ferreira J, Cabrini DA, Campos MM. (2004) Kinin B1 receptors: key G-protein-coupled receptors and their role in inflammatory and painful processes. Br J Pharmacol, 143 (7): 803-18. [PMID:15520046]
Campos MM, Leal PC, Yunes RA, Calixto JB. (2006) Non-peptide antagonists for kinin B1 receptors: new insights into their therapeutic potential for the management of inflammation and pain. Trends Pharmacol Sci, 27 (12): 646-51. [PMID:17056130]
* Couture R, Blaes N, Girolami JP. (2014) Kinin receptors in vascular biology and pathology. Curr Vasc Pharmacol, 12 (2): 223-48. [PMID:24568157]
Couture R, Harrisson M, Vianna RM, Cloutier F. (2001) Kinin receptors in pain and inflammation. Eur J Pharmacol, 429 (1-3): 161-76. [PMID:11698039]
Cruden NL, Newby DE. (2008) Therapeutic potential of icatibant (HOE-140, JE-049). Expert Opin Pharmacother, 9 (13): 2383-90. [PMID:18710362]
Doggrell SA. (2006) Bradykinin B2 receptors as a target in diabetic nephropathy. Curr Opin Investig Drugs, 7 (3): 251-5. [PMID:16555685]
Duchene J, Ahluwalia A. (2009) The kinin B(1) receptor and inflammation: new therapeutic target for cardiovascular disease. Curr Opin Pharmacol, 9 (2): 125-31. [PMID:19124274]
Fortin JP, Marceau F. (2006) Advances in the development of bradykinin receptor ligands. Curr Top Med Chem, 6 (13): 1353-63. [PMID:16918454]
Leeb-Lundberg LM, Marceau F, Müller-Esterl W, Pettibone DJ, Zuraw BL. (2005) International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev, 57 (1): 27-77. [PMID:15734727]
* Marceau F, Bachelard H, Bouthillier J, Fortin JP, Morissette G, Bawolak MT, Charest-Morin X, Gera L. (2020) Bradykinin receptors: Agonists, antagonists, expression, signaling, and adaptation to sustained stimulation. Int Immunopharmacol, 82: 106305 [Epub ahead of print]. [PMID:32106060]
Marceau F, Hess JF, Bachvarov DR. (1998) The B1 receptors for kinins. Pharmacol Rev, 50 (3): 357-86. [PMID:9755287]
Marceau F, Regoli D. (2004) Bradykinin receptor ligands: therapeutic perspectives. Nat Rev Drug Discov, 3 (10): 845-52. [PMID:15459675]
* Paquet JL, Luccarini JM, Fouchet C, Defrêne E, Loillier B, Robert C, Bélichard P, Cremers B, Pruneau D. (1999) Pharmacological characterization of the bradykinin B2 receptor: inter-species variability and dissociation between binding and functional responses. Br J Pharmacol, 126 (5): 1083-90. [PMID:10204994]
Regoli D, Nsa Allogho S, Rizzi A, Gobeil FJ. (1998) Bradykinin receptors and their antagonists. Eur J Pharmacol, 348 (1): 1-10. [PMID:9650825]
Rodi D, Couture R, Ongali B, Simonato M. (2005) Targeting kinin receptors for the treatment of neurological diseases. Curr Pharm Des, 11 (10): 1313-26. [PMID:15853687]
* Thornton E, Ziebell JM, Leonard AV, Vink R. (2010) Kinin receptor antagonists as potential neuroprotective agents in central nervous system injury. Molecules, 15 (9): 6598-618. [PMID:20877247]
Whalley ET, Figueroa CD, Gera L, Bhoola KD. (2012) Discovery and therapeutic potential of kinin receptor antagonists. Expert Opin Drug Discov, 7 (12): 1129-48. [PMID:23095011]
References
1. Amblard M, Daffix I, Bedos P, Bergé G, Pruneau D, Paquet JL, Luccarini JM, Bélichard P, Dodey P, Martinez J. (1999) Design and synthesis of potent bradykinin agonists containing a benzothiazepine moiety. J Med Chem, 42 (20): 4185-92. [PMID:10514288]
2. Aramori I, Zenkoh J, Morikawa N, O'Donnell N, Asano M, Nakamura K, Iwami M, Kojo H, Notsu Y. (1997) Novel subtype-selective nonpeptide bradykinin receptor antagonists FR167344 and FR173657. Mol Pharmacol, 51 (2): 171-6. [PMID:9203620]
3. Audet R, Rioux F, Drapeau G, Marceau F. (1997) Cardiovascular effects of Sar-[D-Phe8]des-Arg9-bradykinin, a metabolically protected agonist of B1 receptor for kinins, in the anesthetized rabbit pretreated with a sublethal dose of bacterial lipopolysaccharide. J Pharmacol Exp Ther, 280 (1): 6-15. [PMID:8996175]
4. Austin CE, Faussner A, Robinson HE, Chakravarty S, Kyle DJ, Bathon JM, Proud D. (1997) Stable expression of the human kinin B1 receptor in Chinese hamster ovary cells. Characterization of ligand binding and effector pathways. J Biol Chem, 272 (17): 11420-5. [PMID:9111052]
5. Bastian S, Loillier B, Paquet JL, Pruneau D. (1997) Stable expression of human kinin B1 receptor in 293 cells: pharmacological and functional characterization. Br J Pharmacol, 122 (2): 393-9. [PMID:9313952]
6. Bélanger S, Bovenzi V, Côté J, Neugebauer W, Amblard M, Martinez J, Lammek B, Savard M, Gobeil Jr F. (2009) Structure-activity relationships of novel peptide agonists of the human bradykinin B2 receptor. Peptides, 30 (4): 777-87. [PMID:19111586]
7. de Sousa Buck H, Ongali B, Thibault G, Lindsey CJ, Couture R. (2002) Autoradiographic detection of kinin receptors in the human medulla of control, hypertensive, and diabetic donors. Can J Physiol Pharmacol, 80 (4): 249-57. [PMID:12025957]
8. Gera L, Fortin JP, Adam A, Stewart JM, Marceau F. (2006) Discovery of a dual-function peptide that combines aminopeptidase N inhibition and kinin B1 receptor antagonism. J Pharmacol Exp Ther, 317: 300-308. [PMID:16368899]
9. Gobeil F, Neugebauer W, Filteau C, Jukic D, Allogho SN, Pheng LH, Nguyen-Le XK, Blouin D, Regoli D. (1996) Structure-activity studies of B1 receptor-related peptides. Antagonists. Hypertension, 28 (5): 833-9. [PMID:8901831]
10. Gobeil F, Pheng LH, Badini I, Nguyen-Le XK, Pizard A, Rizzi A, Blouin D, Regoli D. (1996) Receptors for kinins in the human isolated umbilical vein. Br J Pharmacol, 118 (2): 289-94. [PMID:8735629]
11. Gobeil Jr F, Sirois P, Regoli D. (2014) Preclinical pharmacology, metabolic stability, pharmacokinetics and toxicology of the peptidic kinin B1 receptor antagonist R-954. Peptides, 52: 82-9. [PMID:24361511]
12. Gougat J, Ferrari B, Sarran L, Planchenault C, Poncelet M, Maruani J, Alonso R, Cudennec A, Croci T, Guagnini F et al.. (2004) SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride], a new nonpeptide antagonist of the bradykinin B1 receptor: biochemical and pharmacological characterization. J Pharmacol Exp Ther, 309 (2): 661-9. [PMID:14747609]
13. Hess JF, Borkowski JA, MacNeil T, Stonesifer GY, Fraher J, Strader CD, Ransom RW. (1994) Differential pharmacology of cloned human and mouse B2 bradykinin receptors. Mol Pharmacol, 45: 1-8. [PMID:8302267]
14. Jones C, Phillips E, Davis C, Arbuckle J, Yaqoob M, Burgess GM, Docherty RJ, Webb M, Bevan SJ, McIntyre P. (1999) Molecular characterisation of cloned bradykinin B1 receptors from rat and human. Eur J Pharmacol, 374: 423-433. [PMID:10422787]
15. Leeb-Lundberg LM, Marceau F, Müller-Esterl W, Pettibone DJ, Zuraw BL. (2005) International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev, 57 (1): 27-77. [PMID:15734727]
16. Lesage A, Gibson C, Marceau F, Ambrosi HD, Saupe J, Katzer W, Loenders B, Charest-Morin X, Knolle J. (2020) In Vitro Pharmacological Profile of a New Small Molecule Bradykinin B2 Receptor Antagonist. Front Pharmacol, 11: 916. [PMID:32636746]
17. Lesage A, Marceau F, Gibson C, Loenders B, Katzer W, Ambrosi HD, Saupe J, Faussner A, Pardali E, Knolle J. (2022) In vitro pharmacological profile of PHA-022121, a small molecule bradykinin B2 receptor antagonist in clinical development. Int Immunopharmacol, 105: 108523. [PMID:35086057]
18. Lopes P, Kar S, Chrétien L, Regoli D, Quirion R, Couture R. (1995) Quantitative autoradiographic localization of [125I-Tyr8]bradykinin receptor binding sites in the rat spinal cord: effects of neonatal capsaicin, noradrenergic deafferentation, dorsal rhizotomy and peripheral axotomy. Neuroscience, 68 (3): 867-81. [PMID:8577380]
19. Ongali B, Hellal F, Rodi D, Plotkine M, Marchand-Verrecchia C, Pruneau D, Couture R. (2006) Autoradiographic analysis of mouse brain kinin B1 and B2 receptors after closed head trauma and ability of Anatibant mesylate to cross the blood-brain barrier. J Neurotrauma, 23 (5): 696-707. [PMID:16689671]
20. Pruneau D, Paquet JL, Luccarini JM, Defrêne E, Fouchet C, Franck RM, Loillier B, Robert C, Bélichard P, Duclos H et al.. (1999) Pharmacological profile of LF 16-0687, a new potent non-peptide bradykinin B2 receptor antagonist. Immunopharmacology, 43 (2-3): 187-94. [PMID:10596852]
21. Regoli D, Nsa Allogho S, Rizzi A, Gobeil FJ. (1998) Bradykinin receptors and their antagonists. Eur J Pharmacol, 348 (1): 1-10. [PMID:9650825]
22. Rizzi A, Gobeil F, Calò G, Inamura N, Regoli D. (1997) FR 173657: a new, potent, nonpeptide kinin B2 receptor antagonist. An in vitro study. Hypertension, 29 (4): 951-6. [PMID:9095082]
23. Savard M, Côté J, Tremblay L, Neugebauer W, Regoli D, Gariépy S, Hébert N, Gobeil Jr F. (2016) Safety and pharmacokinetics of a kinin B1 receptor peptide agonist produced with different counter-ions. Biol Chem, 397 (4): 365-72. [PMID:26565554]
24. Savard M, Labonté J, Dubuc C, Neugebauer W, D'Orléans-Juste P, Gobeil Jr F. (2013) Further pharmacological evaluation of a novel synthetic peptide bradykinin B2 receptor agonist. Biol Chem, 394 (3): 353-60. [PMID:23362191]
25. Windischhofer W, Leis HJ. (1997) [3H]bradykinin receptor-binding, receptor-recycling, and receptor-internalization of the B2 bradykinin receptor in the murine osteoblast-like cell line MC3T3-E1. J Bone Miner Res, 12 (10): 1615-25. [PMID:9333122]
26. Zhang SP, Codd EE. (1998) Characterization of bradykinin receptors in human lung fibroblasts using the binding of 3[H][Des-Arg10,Leu9]kallidin and [3H]NPC17731. Life Sci, 62 (25): 2303-14. [PMID:9651119]
27. Zhang SP, Wang HY, Lovenberg TW, Codd EE. (2001) Functional studies of bradykinin receptors in Chinese hamster ovary cells stably expressing the human B2 bradykinin receptor. Int Immunopharmacol, 1 (5): 955-65. [PMID:11379050]
NC-IUPHAR subcommittee and family contributors
Subcommittee members:
Réjean Couture (Chairperson)
Fernand Gobeil Jr |
Other contributors:
Joseph Coulson
Alexander Faussner
Fredrik Leeb-Lundberg
Francois Marceau
Werner Muller-Esterl
Bruce Zuraw |
How to cite this family page
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors. Br J Pharmacol. 180 Suppl 2:S23-S144.
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