Bradykinin receptor B2 explained
Bradykinin receptor B2 is a G-protein coupled receptor for bradykinin, encoded by the BDKRB2 gene in humans.
Mechanism
The B2 receptor (B2R) is a G protein-coupled receptor, probably coupled to Gq and Gi. A 2022 Nature cryo-EM study of human B2R-Gq complexes by Jinkeng Sheng et al. investigated the proximal activation mechanisms of B2R. Sheng et al. propose that upon B2R binding bradykinin or kallidin to a "bulky orthosteric binding pocket," the phenylalanine F8 or F9 residue of bradykinin or kallidin respectively interacts with a "conserved toggle switch" W283. This hydrophobic interaction facilitates the outward movement of transmembrane domain 6 (TM6) of B2R on the cytoplasmic side of the membrane, as well as outward movement of F279, a key residue within the conserved PIF motif of GPCRs (involving proline, isoleucine and phenylalanine). This rearrangement of the PIF motif disrupts the ionic lock formed by the DRY motif and pushes the NPxxY motif towards the activated state, opening an "intracellular cleft" for insertion of the α5-helix of Gq. [1]
Gq stimulates phospholipase C to increase intracellular free calcium and Gi inhibits adenylate cyclase. Furthermore, the receptor stimulates the mitogen-activated protein kinase pathways. It is ubiquitously and constitutively expressed in healthy tissues.
The B2 receptor forms a complex with angiotensin converting enzyme (ACE), and this is thought to play a role in cross-talk between the renin-angiotensin system (RAS) and the kinin–kallikrein system (KKS). The heptapeptide angiotensin (1-7) also potentiates bradykinin action on B2 receptors.[2]
Kallidin also signals through the B2 receptor. An antagonist for the receptor is Hoe 140 (icatibant).[3]
Function
The 9 amino acid bradykinin peptide elicits several responses including vasodilation, edema, smooth muscle spasm and nociceptor stimulation.
Gene
Alternate start codons result in two isoforms of the protein.[4]
See also
Further reading
- Duchêne J, Schanstra J, Cellier E . [30 years: Happy birthday, GPCR. The bradykinin B2 receptor: an alternative and antiproliferative pathway] . Néphrologie . 23 . 1 . 39–41 . 2002 . 11908480 . etal.
- Ariza AC, Bobadilla NA, Halhali A . [Endothelin 1 and angiotensin II in preeeclampsia] . Rev. Invest. Clin. . 59 . 1 . 48–56 . 2007 . 17569300 .
- Hess JF, Borkowski JA, Young GS . Cloning and pharmacological characterization of a human bradykinin (BK-2) receptor. . Biochem. Biophys. Res. Commun. . 184 . 1 . 260–8 . 1992 . 1314587 . 10.1016/0006-291X(92)91187-U . etal.
- Eggerickx D, Raspe E, Bertrand D . Molecular cloning, functional expression and pharmacological characterization of a human bradykinin B2 receptor gene. . Biochem. Biophys. Res. Commun. . 187 . 3 . 1306–13 . 1992 . 1329734 . 10.1016/0006-291X(92)90445-Q . etal.
- Kammerer S, Braun A, Arnold N, Roscher AA . The human bradykinin B2 receptor gene: full length cDNA, genomic organization and identification of the regulatory region. . Biochem. Biophys. Res. Commun. . 211 . 1 . 226–33 . 1995 . 7779089 . 10.1006/bbrc.1995.1800 .
- Braun A, Kammerer S, Böhme E . Identification of polymorphic sites of the human bradykinin B2 receptor gene. . Biochem. Biophys. Res. Commun. . 211 . 1 . 234–40 . 1995 . 7779090 . 10.1006/bbrc.1995.1801 . etal.
- Ma JX, Wang DZ, Ward DC . Structure and chromosomal localization of the gene (BDKRB2) encoding human bradykinin B2 receptor. . Genomics . 23 . 2 . 362–9 . 1995 . 7835885 . 10.1006/geno.1994.1512 . etal. free .
- Powell SJ, Slynn G, Thomas C . Human bradykinin B2 receptor: nucleotide sequence analysis and assignment to chromosome 14. . Genomics . 15 . 2 . 435–8 . 1993 . 7916737 . 10.1006/geno.1993.1084 . etal.
- Menke JG, Borkowski JA, Bierilo KK . Expression cloning of a human B1 bradykinin receptor. . J. Biol. Chem. . 269 . 34 . 21583–6 . 1994 . 10.1016/S0021-9258(17)31844-6 . 8063797 . etal. free .
- Hess JF, Borkowski JA, Macneil T . Differential pharmacology of cloned human and mouse B2 bradykinin receptors. . Mol. Pharmacol. . 45 . 1 . 1–8 . 1994 . 8302267 . etal.
- McIntyre P, Phillips E, Skidmore E . Cloned murine bradykinin receptor exhibits a mixed B1 and B2 pharmacological selectivity. . Mol. Pharmacol. . 44 . 2 . 346–55 . 1993 . 8394991 . etal.
- AbdAlla S, Godovac-Zimmermann J, Braun A . Structure of the bradykinin B2 receptors' amino terminus. . Biochemistry . 35 . 23 . 7514–9 . 1996 . 8652530 . 10.1021/bi9601060 . etal.
- Isami S, Kishikawa H, Araki E . Bradykinin enhances GLUT4 translocation through the increase of insulin receptor tyrosine kinase in primary adipocytes: evidence that bradykinin stimulates the insulin signalling pathway. . Diabetologia . 39 . 4 . 412–20 . 1996 . 8777990 . 10.1007/BF00400672 . 2243985 . etal.
- Dalemar LR, Ivy Jong YJ, Wilhelm B, Baenziger NL . Protein kinases A and C rapidly modulate expression of human lung fibroblast B2 bradykinin receptor affinity forms. . Eur. J. Cell Biol. . 69 . 3 . 236–44 . 1996 . 8900488 .
- Soskic V, Nyakatura E, Roos M . Correlations in palmitoylation and multiple phosphorylation of rat bradykinin B2 receptor in Chinese hamster ovary cells. . J. Biol. Chem. . 274 . 13 . 8539–45 . 1999 . 10085087 . 10.1074/jbc.274.13.8539 . etal. free .
- Cassano G, Susca F, Lippe C, Guanti G . Two B1 and B2 bradykinin receptor antagonists fail to inhibit the Ca2+ response elicited by bradykinin in human skin fibroblasts. . Gen. Pharmacol. . 32 . 2 . 239–44 . 1999 . 10188626 . 10.1016/S0306-3623(98)00275-4 .
- Efremov R, Truong MJ, Darcissac EC . Human chemokine receptors CCR5, CCR3 and CCR2B share common polarity motif in the first extracellular loop with other human G-protein coupled receptors implications for HIV-1 coreceptor function. . Eur. J. Biochem. . 263 . 3 . 746–56 . 1999 . 10469138 . 10.1046/j.1432-1327.1999.00553.x . etal.
- Marrero MB, Venema VJ, Ju H . Endothelial nitric oxide synthase interactions with G-protein-coupled receptors. . Biochem. J. . 343 . 2. 335–40 . 1999 . 10510297 . 10.1042/0264-6021:3430335 . 1220558 . etal.
- Reyes-Cruz G, Vázquez-Prado J, Müller-Esterl W, Vaca L . Regulation of the human bradykinin B2 receptor expressed in sf21 insect cells: a possible role for tyrosine kinases . J. Cell. Biochem. . 76 . 4 . 658–73 . 2000 . 10653985 . 10.1002/(SICI)1097-4644(20000315)76:4<658::AID-JCB14>3.0.CO;2-7 . 30042149 .
- Golser R, Gorren AC, Leber A . Interaction of endothelial and neuronal nitric-oxide synthases with the bradykinin B2 receptor. Binding of an inhibitory peptide to the oxygenase domain blocks uncoupled NADPH oxidation . J. Biol. Chem. . 275 . 8 . 5291–6 . 2000 . 10681501 . 10.1074/jbc.275.8.5291 . etal. free .
External links
- Web site: Bradykinin Receptors: B2 . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology .
Notes and References
- 10.1038/s41467-022-28399-1 . Cryo-EM structures of human bradykinin receptor-Gq proteins complexes . 2022 . Shen . Jinkang . Zhang . Dongqi . Fu . Yao . Chen . Anqi . Yang . Xiaoli . Zhang . Haitao . Nature Communications . 13 . 1 . 714 . 35132089 . 8821558 . 2022NatCo..13..714S .
- Fernandes L, Fortes ZB, Nigro D, Tostes RC, Santos RA, Catelli De Carvalho MH . Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo . Hypertension . 37 . 2 Part 2 . 703–9 . 2001 . 11230360 . 10.1161/01.hyp.37.2.703 . 17827058 .
- Hoe 140 a new potent and long acting bradykinin-antagonist: in vivo studies . 1917928 . 1364852 . 102 . 1991 . Br. J. Pharmacol. . 774–7 . Wirth K, Hock FJ, Albus U, Linz W, Alpermann HG, Anagnostopoulos H, Henk S, Breipohl G, König W, Knolle J . 3 . 10.1111/j.1476-5381.1991.tb12249.x.
- Web site: Entrez Gene: BDKRB2 bradykinin receptor B2.