Bradykinin receptor B2

Identifiers

BDKRB2 ; B2R; BK-2; BK2; BKR2; BRB2

External IDs

OMIM: 113503 MGI: 102845 HomoloGene: 519 IUPHAR: 42 ChEMBL: 3157 GeneCards: BDKRB2 Gene

Gene ontology
Molecular function	• protease binding • phosphatidylinositol phospholipase C activity • bradykinin receptor activity • protein binding • beta-2 adrenergic receptor binding • type 1 angiotensin receptor binding • protein heterodimerization activity
Cellular component	• endosome • cytosol • plasma membrane • integral component of plasma membrane
Biological process	• acute inflammatory response to antigenic stimulus • smooth muscle contraction • inflammatory response • cell surface receptor signaling pathway • transmembrane receptor protein tyrosine kinase signaling pathway • G-protein coupled receptor signaling pathway • positive regulation of cytosolic calcium ion concentration • blood circulation • negative regulation of cell proliferation • response to salt stress • regulation of vasoconstriction • negative regulation of peptidyl-serine phosphorylation • maintenance of blood-brain barrier • vasoconstriction • vasodilation • response to drug • regulation of vascular permeability • negative regulation of blood pressure • arachidonic acid secretion • cellular response to hypoxia • negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

624

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 14:
96.2 – 96.24 Mb

Chr 12:
105.56 – 105.59 Mb

PubMed search

Bradykinin receptor B₂ is a G-protein coupled receptor for bradykinin, encoded by the BDKRB2 gene in humans.

Mechanism

The B₂ receptor is a G protein-coupled receptor, probably coupled to G_q and G_i. G_q stimulates phospholipase C to increase intracellular free calcium and G_i 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 (A1-7) also potentiates bradykinin action on B₂ receptors.^[1]

Kallidin also signals through the B₂ receptor. An antagonist for the receptor is Hoe 140 (icatibant). ^[2]

Function

The 9 amino acid bradykinin peptide elicits many responses including vasodilation, edema, smooth muscle spasm and pain fiber stimulation.

Gene

Alternate start codons result in two isoforms of the protein.^[3]

References

↑ Fernandes L, Fortes ZB, Nigro D, Tostes RC, Santos RA, Catelli De Carvalho MH (2001). "Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo". Hypertension 37 (2 Part 2): 703–9. doi:10.1161/01.hyp.37.2.703. PMID 11230360.
↑ "Hoe 140 a new potent and long acting bradykinin-antagonist: in vivo studies".
↑ "Entrez Gene: BDKRB2 bradykinin receptor B2".

External links

"Bradykinin Receptors: B₂". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

Duchêne J, Schanstra J, Cellier E; et al. (2002). "[30 years: Happy birthday, GPCR. The bradykinin B2 receptor: an alternative and antiproliferative pathway]". Néphrologie 23 (1): 39–41. PMID 11908480.
Ariza AC, Bobadilla NA, Halhali A (2007). "[Endothelin 1 and angiotensin II in preeeclampsia]". Rev. Invest. Clin. 59 (1): 48–56. PMID 17569300.
Hess JF, Borkowski JA, Young GS; et al. (1992). "Cloning and pharmacological characterization of a human bradykinin (BK-2) receptor.". Biochem. Biophys. Res. Commun. 184 (1): 260–8. doi:10.1016/0006-291X(92)91187-U. PMID 1314587.
Eggerickx D, Raspe E, Bertrand D; et al. (1992). "Molecular cloning, functional expression and pharmacological characterization of a human bradykinin B2 receptor gene.". Biochem. Biophys. Res. Commun. 187 (3): 1306–13. doi:10.1016/0006-291X(92)90445-Q. PMID 1329734.
Kammerer S, Braun A, Arnold N, Roscher AA (1995). "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. doi:10.1006/bbrc.1995.1800. PMID 7779089.
Braun A, Kammerer S, Böhme E; et al. (1995). "Identification of polymorphic sites of the human bradykinin B2 receptor gene.". Biochem. Biophys. Res. Commun. 211 (1): 234–40. doi:10.1006/bbrc.1995.1801. PMID 7779090.
Ma JX, Wang DZ, Ward DC; et al. (1995). "Structure and chromosomal localization of the gene (BDKRB2) encoding human bradykinin B2 receptor.". Genomics 23 (2): 362–9. doi:10.1006/geno.1994.1512. PMID 7835885.
Powell SJ, Slynn G, Thomas C; et al. (1993). "Human bradykinin B2 receptor: nucleotide sequence analysis and assignment to chromosome 14.". Genomics 15 (2): 435–8. doi:10.1006/geno.1993.1084. PMID 7916737.
Menke JG, Borkowski JA, Bierilo KK; et al. (1994). "Expression cloning of a human B1 bradykinin receptor.". J. Biol. Chem. 269 (34): 21583–6. PMID 8063797.
Hess JF, Borkowski JA, Macneil T; et al. (1994). "Differential pharmacology of cloned human and mouse B2 bradykinin receptors.". Mol. Pharmacol. 45 (1): 1–8. PMID 8302267.
McIntyre P, Phillips E, Skidmore E; et al. (1993). "Cloned murine bradykinin receptor exhibits a mixed B1 and B2 pharmacological selectivity.". Mol. Pharmacol. 44 (2): 346–55. PMID 8394991.
AbdAlla S, Godovac-Zimmermann J, Braun A; et al. (1996). "Structure of the bradykinin B2 receptors' amino terminus.". Biochemistry 35 (23): 7514–9. doi:10.1021/bi9601060. PMID 8652530.
Isami S, Kishikawa H, Araki E; et al. (1996). "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. doi:10.1007/BF00400672. PMID 8777990.
Dalemar LR, Ivy Jong YJ, Wilhelm B, Baenziger NL (1996). "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. PMID 8900488.
Soskic V, Nyakatura E, Roos M; et al. (1999). "Correlations in palmitoylation and multiple phosphorylation of rat bradykinin B2 receptor in Chinese hamster ovary cells.". J. Biol. Chem. 274 (13): 8539–45. doi:10.1074/jbc.274.13.8539. PMID 10085087.
Cassano G, Susca F, Lippe C, Guanti G (1999). "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. doi:10.1016/S0306-3623(98)00275-4. PMID 10188626.
Efremov R, Truong MJ, Darcissac EC; et al. (1999). "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. doi:10.1046/j.1432-1327.1999.00553.x. PMID 10469138.
Marrero MB, Venema VJ, Ju H; et al. (1999). "Endothelial nitric oxide synthase interactions with G-protein-coupled receptors.". Biochem. J. 343 Pt 2 (2): 335–40. doi:10.1042/0264-6021:3430335. PMC 1220558. PMID 10510297.
Reyes-Cruz G, Vázquez-Prado J, Müller-Esterl W, Vaca L (2000). "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. doi:10.1002/(SICI)1097-4644(20000315)76:4<658::AID-JCB14>3.0.CO;2-7. PMID 10653985.
Golser R, Gorren AC, Leber A; et al. (2000). "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. doi:10.1074/jbc.275.8.5291. PMID 10681501.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Adhesion	ADGRG (1 2 3 4 5 6 7)

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

Neuropeptide receptors

G protein-coupled receptor

Hormone receptors

Hypothalamic	CRH FSH LHRH TRH Somatostatin

Pituitary	Vasopressin 1A 1B 2 Oxytocin LHCG TSH

Other	Atrial natriuretic factor NPR3 Calcitonin Cholecystokinin A B VIP

Opioid receptors

Other neuropeptide receptors

Type I cytokine receptor

GH
Prolactin

Enzyme-linked receptor

Atrial natriuretic factor
- NPR1
- NPR2

Other

Sigma
- 1
- 2

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