Overview: Bradykinin (or kinin) receptors [nomenclature recommended by the NC-IUPHAR subcommittee on bradykinin (kinin) receptors, Leeb-Lundberg et al., 2005] are activated by the endogenous peptides bradykinin (BK), [des-Arg9]BK, Lys-BK (kallidin), Lys-[des-Arg9]BK, T-kinin (Ile-Ser-BK), [Hyp3]BK and Lys-[Hyp3]BK. The variation in affinity or inactivity of B2 receptor antagonists could reflect the existence of species homologues of B2 receptors.
| Nomenclature | B1 | B2 |
| Ensembl ID | ENSG00000100739 | ENSG00000168398 |
| Principal transduction | Gq/11 | Gq/11 |
| Rank order of potency | Lys-[des-Arg9]BK > [des-Arg9]BK = Lys-BK > BK | Lys-BK ≥ BK >> [des-Arg9]BK, Lys-[des-Arg9]BK |
| Selective agonists | Lys-[des-Arg9]BK, Sar[DPhe8][des-Arg9]BK | [Phe8,ψ(CH2-NH)Arg9]BK, [Hyp3,Tyr(Me)8]BK |
| Selective antagonists | B9958 (9.2, Regoli et al., 1998), R914 (8.6, Gobeil et al., 1999), R715 (8.5, Gobeil et al., 1996a), Lys-[Leu8][des-Arg9]BK (8.0) | Icatibant (8.4, Gobeil et al., 1996b), FR173657 (8.2, Rizzi et al., 1997), LF160687 (Pruneau et al., 1999) |
| Probes | [3H]-Lys-[des-Arg9]BK (0.4 nM), [3H]-Lys-[Leu8][des-Arg9]BK, [125I]-Hpp-desArg9HOE140 (0.1 nM) | [3H]-BK (0.2 nM), [3H]-NPC17731 (50–900 pM), [125I]-[Tyr8]BK |
Glossary
Abbreviations:
- B9958
Lys-Lys[Hyp3,Cpg5,dTic7,Cpg8][des-Arg9]BK
- FR173657
(E)-3-(6-acetamido-3-pyridyl)-N-(N-[2,4-dichloro-3{(2-methyl-8-quinolinyl)oxymethyl} phenyl]-N-methylaminocarbonyl-methyl)acrylamide
- Icatibant
DArg[Hyp3,Thi5,DTic7,Oic8]BK, also known as HOE140
- LF160687
1-([2,4-dichloro-3-{([2,4-dimethylquinolin-8-yl]oxy)methyl}phenyl]sulfonyl)-N-(3-[{4-(aminoimethyl)phenyl}carbonylamino]propyl)-2(S)-pyrrolidinecarboxamide
- NPC17731
DArg[Hyp3,DHypE(transpropyl)7,Oic8]BK
- R715
AcLys[D Nal7,Ile8][des-Arg9]BK
- R914
AcLys-Lys-([αMe]Phe5δ-βNal7,Ile8)desArg9BK
Further Reading
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 Pharmacol143: 803–818.
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 Sci27: 646–651.
Couture R, Harrison M, Vianna RM, Cloutier F (2001). Kinin receptors in pain and inflammation. Eur J Pharmacol429: 161–176.
Cruden NL, Newby DE (2008). Therapeutic potential of icatibant (HOE-140, JE-049). Expert Opin Pharmacother9: 2383–2390.
Doggrell SA (2006). Bradykinin B2 receptors as a target in diabetic nephropathy. Curr Opin Investig Drugs7: 251–255.
Fortin JP, Marceau FO (2006). Advances in the development of bradykinin ligands. Curr Top Med Chem6: 1353–1363.
Leeb-Lundberg LMF, Marceau F, Muller-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 Rev57: 27–77.
Marceau F, Regoli D (2004). Bradykinin receptor ligands: Therapeutic perspectives. Nature Rev Drug Discov3: 845–852.
Marceau F, Hess JF, Bachvarov DR (1998). The B-1 receptors for kinins. Pharmacol Rev50: 357–386.
Regoli D, Allogho SN, Rizzi A, Gobeil FJ (1998). Bradykinin receptors and their antagonists. Eur J Pharmacol 348: 1–10.
Rodi D, Couture R, Ongali B, Simonato M (2005). Targeting kinin receptors for the treatment of neurological diseases. Curr Pharm Des11: 1313–1326.
References
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