Genomes and Genes
bradykinin b2 receptor
Summary: A constitutively expressed subtype of bradykinin receptor that may play a role in the acute phase of the inflammatory and pain response. It has high specificity for intact forms of BRADYKININ and KALLIDIN. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.
- Saifudeen Z, Dipp S, Fan H, El Dahr S. Combinatorial control of the bradykinin B2 receptor promoter by p53, CREB, KLF-4, and CBP: implications for terminal nephron differentiation. Am J Physiol Renal Physiol. 2005;288:F899-909 pubmed..The bradykinin B2 receptor (B2R) regulates renal function and integrity, and its expression is induced during terminal nephron ..
- Leeb Lundberg L, Marceau F, Muller Esterl W, Pettibone D, Zuraw B. International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev. 2005;57:27-77 pubmed..This review is a comprehensive presentation of our current understanding of these receptors in terms of molecular and cell biology, physiology, pharmacology, and involvement in human disease and drug development. ..
- Ikeda Y, Hayashi I, Kamoshita E, Yamazaki A, Endo H, Ishihara K, et al. Host stromal bradykinin B2 receptor signaling facilitates tumor-associated angiogenesis and tumor growth. Cancer Res. 2004;64:5178-85 pubmed..These results suggest that BK generated from kininogens supplied from the host may facilitate tumor-associated angiogenesis and tumor growth by stimulating stromal B(2) signaling to up-regulate VEGF production mainly in fibroblasts. ..
- Marney A, Ma J, Luther J, Ikizler T, Brown N. Endogenous bradykinin contributes to increased plasminogen activator inhibitor 1 antigen following hemodialysis. J Am Soc Nephrol. 2009;20:2246-52 pubmed publisher..Factors that increase the production of bradykinin or decrease its degradation may enhance the inflammatory response to hemodialysis. ..
- Hellal F, Pruneau D, Palmier B, Faye P, Croci N, Plotkine M, et al. Detrimental role of bradykinin B2 receptor in a murine model of diffuse brain injury. J Neurotrauma. 2003;20:841-51 pubmedInhibition of the bradykinin B2 receptor type (B2R) has been shown to improve neurological outcome in models of focal traumatic brain injury. However, the involvement of B2R in trauma-induced diffuse injury has not yet been explored...
- Gröger M, Lebesgue D, Pruneau D, Relton J, Kim S, Nussberger J, et al. Release of bradykinin and expression of kinin B2 receptors in the brain: role for cell death and brain edema formation after focal cerebral ischemia in mice. J Cereb Blood Flow Metab. 2005;25:978-89 pubmedPharmacological studies using bradykinin B2 receptor antagonists suggest that bradykinin, an early mediator of inflammation and the main metabolite of the kallikrein-kinin system, is involved in secondary brain damage after cerebral ..
- Zhang Y, Adner M, Cardell L. Up-regulation of bradykinin receptors in a murine in-vitro model of chronic airway inflammation. Eur J Pharmacol. 2004;489:117-26 pubmed..Thus, TNF-alpha causes an increase of bradykinin contractility in mouse trachea, which at least partly is due to a transcriptional increase of bradykinin receptors. ..
- Abadir P, Periasamy A, Carey R, Siragy H. Angiotensin II type 2 receptor-bradykinin B2 receptor functional heterodimerization. Hypertension. 2006;48:316-22 pubmed..Controlling the expression of AT2R-B2R, consequently influencing their biologically active dimerization, presents a potential therapeutic target for the treatment of hypertension and other cardiovascular and renal disorders. ..
- Monteiro A, Schmitz V, Svensjo E, Gazzinelli R, Almeida I, Todorov A, et al. Cooperative activation of TLR2 and bradykinin B2 receptor is required for induction of type 1 immunity in a mouse model of subcutaneous infection by Trypanosoma cruzi. J Immunol. 2006;177:6325-35 pubmed..In summary, we have described a s.c. infection model where type 1 immunity is vigorously up-regulated by bradykinin, an innate signal whose levels in peripheral tissues are controlled by an intricate interplay of TLR2, B(2)R, and ACE. ..
- Lee C, Shieh D, Tzeng C, Chen C, Wang S, Chiu Y, et al. Bradykinin-induced IL-6 expression through bradykinin B2 receptor, phospholipase C, protein kinase Cdelta and NF-kappaB pathway in human synovial fibroblasts. Mol Immunol. 2008;45:3693-702 pubmed publisher..Our results suggest that BK increased IL-6 production in synovial fibroblasts via the B2 BK receptor/PI-PLC/PKCdelta/and NF-kappaB signaling pathway. ..
- Zhang Y, Adner M, Cardell L. IL-1beta-induced transcriptional up-regulation of bradykinin B1 and B2 receptors in murine airways. Am J Respir Cell Mol Biol. 2007;36:697-705 pubmed..Intracellular JNK pathway and TNF-alpha might provide key links between inflammatory mediators like IL-1beta and airway hyperresponsiveness to bradykinin. ..
- Fu Y, Katsuya T, Matsuo A, Yamamoto K, Akasaka H, Takami Y, et al. Relationship of bradykinin B2 receptor gene polymorphism with essential hypertension and left ventricular hypertrophy. Hypertens Res. 2004;27:933-8 pubmedThe bradykinin B2 receptor shows a protective role in the development of hypertension and renal and cardiovascular complications...
- Niu W, Qi Y, Gao P, Zhu D. A meta-analysis of the bradykinin B2 receptor gene --58C/T polymorphism with hypertension. Clin Chim Acta. 2010;411:324-8 pubmed publisherNumerous studies have attempted to associate -58C/T polymorphism of bradykinin B2 receptor gene (BDKRB2) with hypertension, whereas results were often irreproducible...
- Shen B, Harrison Bernard L, Fuller A, Vanderpool V, Saifudeen Z, El Dahr S. The Bradykinin B2 receptor gene is a target of angiotensin II type 1 receptor signaling. J Am Soc Nephrol. 2007;18:1140-9 pubmed..It was demonstrated that the bradykinin B2 receptor gene (BdkrB2) is a direct transcriptional target of the angiotensin II (AngII) type 1 receptor (AT(1)R) in ..
- Fallo F, Mulatero P, Vettor R, Scarda A, Della Mea P, Morello F, et al. Bradykinin B2 receptor gene C-58T polymorphism and insulin resistance. A study on obese patients. Horm Metab Res. 2004;36:243-6 pubmedThe bradykinin B2 receptor (B2R) gene is a candidate in the pathogenesis of insulin resistance, which often clusters with other abnormalities in metabolic syndrome...
- Russell F, Veldhoen V, Tchitchkan D, McDougall J. Proteinase-activated receptor-4 (PAR4) activation leads to sensitization of rat joint primary afferents via a bradykinin B2 receptor-dependent mechanism. J Neurophysiol. 2010;103:155-63 pubmed publisher..This PAR(4)-induced sensitization is TRPV1-independent but involves B(2) receptor activation, suggesting a role for kinins in this process. ..
- Brechter A, Persson E, Lundgren I, Lerner U. 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;43:72-83 pubmed publisher..These mechanisms might help to explain the enhanced bone resorption associated with inflammatory disorders, including periodontitis and rheumatoid arthritis. ..
- Woo S, Bang S, Chung M, Jin S, Kim Y, Lee S. Lack of association between ACE and bradykinin B2 receptor gene polymorphisms and ACE inhibitor-induced coughing in hypertensive Koreans. J Clin Pharm Ther. 2009;34:561-7 pubmed publisher..for any associations between ACE inhibitor-induced coughing and polymorphisms in the genes for ACE and the bradykinin B2 receptor, which are suspected to be related to coughing...
- Corthorn J, Germain A, Chacón C, Rey S, Soto G, Figueroa C, et al. Expression of kallikrein, bradykinin b2 receptor, and endothelial nitric oxide synthase in placenta in normal gestation, preeclampsia, and placenta accreta. Endocrine. 2006;29:491-9 pubmed..accreta/exaggerated invasion (n = 6), we performed semiquantitative immunohistochemistry for kallikrein, bradykinin B2 receptor, and endothelial nitric oxide synthase (eNOS)...
- Zausinger S, Lumenta D, Pruneau D, Schmid Elsaesser R, Plesnila N, Baethmann A. Therapeutical efficacy of a novel non-peptide bradykinin B2 receptor antagonist on brain edema formation and ischemic tissue damage in focal cerebral ischemia. Acta Neurochir Suppl. 2003;86:205-7 pubmed..We currently studied neuroprotective properties of a bradykinin B2 receptor antagonist (LF16-0687 Ms) in transitory focal cerebral ischemia to assess infarct formation and the ..
- Zweckberger K, Plesnila N. Anatibant, a selective non-peptide bradykinin B2 receptor antagonist, reduces intracranial hypertension and histopathological damage after experimental traumatic brain injury. Neurosci Lett. 2009;454:115-7 pubmed publisher..Anatibant (LF 16-0687), a selective non-peptide bradykinin B2 receptor antagonist, reduces brain edema after experimental TBI, however, so far no data are available if Anatibant ..
- Dlamini Z, Bhoola K. Upregulation of tissue kallikrein, kinin B1 receptor, and kinin B2 receptor in mast and giant cells infiltrating oesophageal squamous cell carcinoma. J Clin Pathol. 2005;58:915-22 pubmed
- Kaman W, Wolterink A, Bader M, Boele L, van der Kleij D. The bradykinin B2 receptor in the early immune response against Listeria infection. Med Microbiol Immunol. 2009;198:39-46 pubmed publisher..Thus, we show that bradykinin and the B(2)R play a role in early innate immune functions during bacterial infection. ..
- Shirasaki H, Kanaizumi E, Himi T. Immunohistochemical localization of the bradykinin B1 and B2 receptors in human nasal mucosa. Mediators Inflamm. 2009;2009:102406 pubmed publisher..The results may have an important clinical implication for understanding the differential roles of BK receptor subtypes on upper airway diseases such as allergic rhinitis and nonallergic rhinitis. ..
- Xia C, Smith R, Shen B, Yang Z, Borlongan C, Chao L, et al. Postischemic brain injury is exacerbated in mice lacking the kinin B2 receptor. Hypertension. 2006;47:752-61 pubmed..These results indicate that the kinin B2 receptor promotes survival and protects against brain injury by suppression of apoptosis and inflammation induced by ischemic stroke. ..
- Mukhin Y, Gooz M, Raymond J, Garnovskaya M. Collagenase-2 and -3 mediate epidermal growth factor receptor transactivation by bradykinin B2 receptor in kidney cells. J Pharmacol Exp Ther. 2006;318:1033-43 pubmed..This study demonstrates a novel role for collagenase-2 and -3 in signaling of the G(q)-coupled BK B(2) receptor in mIMCD-3 cells. ..
- Srinivasan D, Kosaka A, Daniels D, Ford A, Bhattacharya A. Pharmacological and functional characterization of bradykinin B2 receptor in human prostate. Eur J Pharmacol. 2004;504:155-67 pubmed..curves in human prostate stromal cells with apparent estimate of affinity similar to that for the human bradykinin B2 receptor. Bradykinin (10 nM) caused proliferation of prostate stromal cells and phosphorylated extracellular signal-..
- Cunha T, Verri W, Fukada S, Guerrero A, Santodomingo Garzon T, Poole S, et al. TNF-alpha and IL-1beta mediate inflammatory hypernociception in mice triggered by B1 but not B2 kinin receptor. Eur J Pharmacol. 2007;573:221-9 pubmed..On the other hand, in LPS-primed mice, the B(1) kinin receptor mediates hypernociception by a mechanism dependent on TNF-alpha and IL-1beta, which could stimulate prostanoid and sympathetic amine production. ..
- Souza D, Lomez E, Pinho V, Pesquero J, Bader M, Pesquero J, et al. Role of bradykinin B2 and B1 receptors in the local, remote, and systemic inflammatory responses that follow intestinal ischemia and reperfusion injury. J Immunol. 2004;172:2542-8 pubmed..Blockade of B(1)Rs could be a more effective strategy than B(2) or B(1)/B(2) receptor blockade for the treatment of the inflammatory injuries that follow I/R. ..
- Brunius G, Domeij H, Gustavsson A, Yucel Lindberg T. Bradykinin upregulates IL-8 production in human gingival fibroblasts stimulated by interleukin-1beta and tumor necrosis factor alpha. Regul Pept. 2005;126:183-8 pubmed..This stimulatory effect of BK on IL-8 production may contribute to the maintenance of the gingival inflammation and enhanced risk for destruction of gingival connective tissue. ..
- Jozwiak L, Drop A, Buraczynska K, Ksiazek P, Mierzicki P, Buraczynska M. Association of the human bradykinin B2 receptor gene with chronic renal failure. Mol Diagn. 2004;8:157-61 pubmed..We did not confirm the previously published reports that the B2R gene polymorphism has a protective role in the development of ESRD. ..
- Chiang W, Chien C, Lin W, Lin S, Chen Y, Lai C, et al. Early activation of bradykinin B2 receptor aggravates reactive oxygen species generation and renal damage in ischemia/reperfusion injury. Free Radic Biol Med. 2006;41:1304-14 pubmed..The deleterious effects of kallikrein on ischemia/reperfusion injury were reversed by cotreatment with bradykinin B2 receptor (B2R) antagonist, but not B1 receptor antagonist, and were not associated with hemodynamic changes...
- Christiansen S, Eddleston J, Woessner K, Chambers S, Ye R, Pan Z, et al. Up-regulation of functional kinin B1 receptors in allergic airway inflammation. J Immunol. 2002;169:2054-60 pubmed..Taken together, these results show that functional B1 receptors are induced in the airway during allergic inflammation and suggest that they participate in the regulation of gene expression. ..
- Mukae S, Itoh S, Aoki S, Iwata T, Nishio K, Sato R, et al. Association of polymorphisms of the renin-angiotensin system and bradykinin B2 receptor with ACE-inhibitor-related cough. J Hum Hypertens. 2002;16:857-63 pubmed..of ACE insertion/deletion (I/D), angiotensin II type 1 receptor (1166A/C), type 2 receptor (3123C/A), and bradykinin B2 receptor (-58T/C, exon 1, I/D), were analyzed in these subjects...
- Haasemann M, Cartaud J, Muller Esterl W, Dunia I. Agonist-induced redistribution of bradykinin B2 receptor in caveolae. J Cell Sci. 1998;111 ( Pt 7):917-28 pubmed..We have applied immunocytochemical methods to localize the bradykinin B2 receptor and to examine its agonist induced redistribution in A431 cells...
- Cassim B, Naidoo S, Ramsaroop R, Bhoola K. Immunolocalization of bradykinin receptors on human synovial tissue. Immunopharmacology. 1997;36:121-5 pubmed..However, further studies are required to assess the role of B1 receptors in active joint inflammation. ..
- Imamura T, Tanase S, Hayashi I, Potempa J, Kozik A, Travis J. Release of a new vascular permeability enhancing peptide from kininogens by human neutrophil elastase. Biochem Biophys Res Commun. 2002;294:423-8 pubmed..The molecular mechanism for neutrophil-associated VPE may be explained by excision of E-kinin from kininogens by NE, followed by further processing of the peptide. ..
- Lee Y, Tsai J. Angiotensin-converting enzyme gene insertion/deletion, not bradykinin B2 receptor -58T/C gene polymorphism, associated with angiotensin-converting enzyme inhibitor-related cough in Chinese female patients with non-insulin-dependent diabetes mellitus. Metabolism. 2001;50:1346-50 pubmed..12; df = 2; P <.001). There was no association between the bradykinin B2 receptor gene -58T/C polymorphism with ACEI-related cough...
- Blaukat A, Pizard A, Breit A, Wernstedt C, Alhenc Gelas F, Muller Esterl W, et al. Determination of bradykinin B2 receptor in vivo phosphorylation sites and their role in receptor function. J Biol Chem. 2001;276:40431-40 pubmed..32P labeling and phosphopeptide sequencing we provide a complete phosphorylation map of the human bradykinin B2 receptor in its native cellular environment...
- McLean P, Ahluwalia A, Perretti M. Association between kinin B(1) receptor expression and leukocyte trafficking across mouse mesenteric postcapillary venules. J Exp Med. 2000;192:367-80 pubmed..This involves activation of C fibers and mast cells, release of substance P and histamine, and stimulation of NK(1), NK(3), and H(1) receptors. ..
- Raidoo D, Sawant S, Mahabeer R, Bhoola K. Kinin receptors are expressed in human astrocytic tumour cells. Immunopharmacology. 1999;43:255-63 pubmed..The immunoreactive B2 receptors were located closer to the periphery of the tumour cells while B1 immunolabeling was observed throughout the cell. ..
- Valdes G, Germain A, Corthorn J, Chacon C, Figueroa C, Muller Esterl W. Tissue kallikrein and bradykinin B2 receptor in human uterus in luteal phase and in early and late gestation. Endocrine. 2001;16:207-15 pubmed
- Kusser B, Braun A, Praun M, Illi S, von Mutius E, Roscher A. Polymorphisms in the bradykinin B2 receptor gene and childhood asthma. Biol Chem. 2001;382:885-9 pubmed..05). Since BE1-2G has previously been shown to lead to a higher transcription rate of the B2 receptor, this result warrants further investigation of the role of bradykinin in conferring susceptibility to pediatric asthma. ..
- Golser R, Gorren A, Leber A, Andrew P, Habisch H, Werner E, et al. 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. 2000;275:5291-6 pubmed..This interaction of nNOS with the B2R may recruit the enzyme to allow for the effective coupling of bradykinin signaling to the nitric oxide pathway. ..
- Thuringer D, Maulon L, Frelin C. Rapid transactivation of the vascular endothelial growth factor receptor KDR/Flk-1 by the bradykinin B2 receptor contributes to endothelial nitric-oxide synthase activation in cardiac capillary endothelial cells. J Biol Chem. 2002;277:2028-32 pubmed..This represents a novel mechanism whereby a G protein-coupled receptor activates a receptor tyrosine kinase to generate biological response. ..
- Scharfstein J, Schmitz V, Morandi V, Capella M, Lima A, Morrot A, et al. Host cell invasion by Trypanosoma cruzi is potentiated by activation of bradykinin B(2) receptors. J Exp Med. 2000;192:1289-300 pubmed
- Monsees T, Blöcher S, Heidorn F, Winkler A, Siems W, Muller Esterl W, et al. Expression and location of the bradykinin B2 receptor in rat testis. Biol Reprod. 2002;67:1832-9 pubmed..The results point to a possible function of the tissue kallikrein-kinin system in the local regulation of spermatogenesis. ..
- Miura S, Matsuo Y, Saku K. Transactivation of KDR/Flk-1 by the B2 receptor induces tube formation in human coronary endothelial cells. Hypertension. 2003;41:1118-23 pubmed..To our knowledge, this is a novel mechanism in which transactivation of KDR/Flk-1 by a G protein-coupled receptor, B2 receptor, may be a potent signal for tube formation. ..
- Pal Ghosh R, Yu J, Prado G, Taylor L, Mierke D, Polgar P. Chimeric exchanges within the bradykinin B2 receptor intracellular face with the prostaglandin EP2 receptor as the donor: importance of the second intracellular loop for cAMP synthesis. Arch Biochem Biophys. 2003;415:54-62 pubmed..Additionally, our results confirm the importance of the distal C terminus in determining receptor uptake. ..
- Braun A, Kammerer S, Bohme E, Muller B, Roscher A. Identification of polymorphic sites of the human bradykinin B2 receptor gene. Biochem Biophys Res Commun. 1995;211:234-40 pubmed..These new genetic markers provide valuable tools to elucidate a potential role of a hereditary dysfunction of the B2 bradykinin receptor gene in disorders such as hypertension or ischemic heart disease. ..