Genomes and Genes
bradykinin b1 receptor
Summary: A subtype of BRADYKININ RECEPTOR that is induced in response to INFLAMMATION. It may play a role in chronic inflammation and has a high specificity for KININS lacking the C-terminal ARGININE such as des-Arg(10)-kallidin and des-Arg(9)-bradykinin. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.
- Kakoki M, McGarrah R, Kim H, Smithies O. Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury. Proc Natl Acad Sci U S A. 2007;104:7576-81 pubmed..Thus, both the B1 and B2 bradykinin receptors play an important role in reducing DNA damage, apoptosis, morphological and functional kidney changes, and mortality during renal ischemia/reperfusion injury. ..
- El Midaoui A, Ongali B, Petcu M, Rodi D, de Champlain J, Neugebauer W, et al. Increases of spinal kinin receptor binding sites in two rat models of insulin resistance. Peptides. 2005;26:1323-30 pubmed..Results show that chronic hyperglycemia associated with insulin resistance increases B1 and B2 receptor binding sites in the rat spinal cord through distinct mechanisms, including the oxidative stress for the B1 receptor. ..
- 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. ..
- Ongali B, Campos M, Petcu M, Rodi D, Cloutier F, Chabot J, et al. Expression of kinin B1 receptors in the spinal cord of streptozotocin-diabetic rat. Neuroreport. 2004;15:2463-6 pubmed..Levels of mRNA were significantly increased (+68%) at 2 and 7 days but not at 21 days. These data bring the first molecular evidence for an early up-regulation of B1R in the spinal cord of diabetic rat. ..
- Passos G, Fernandes E, Campos M, Araújo J, Pesquero J, Souza G, et al. Kinin B1 receptor up-regulation after lipopolysaccharide administration: role of proinflammatory cytokines and neutrophil influx. J Immunol. 2004;172:1839-47 pubmed
- Liesmaa I, Kuoppala A, Shiota N, Kokkonen J, Kostner K, Mayranpaa M, et al. Increased expression of bradykinin type-1 receptors in endothelium of intramyocardial coronary vessels in human failing hearts. Am J Physiol Heart Circ Physiol. 2005;288:H2317-22 pubmed..These novel results show that BK-1Rs are induced in the endothelium of intramyocardial coronary vessels in failing human hearts and so may participate in the pathogenesis of heart failure. ..
- Gama Landgraf R, Jancar S, Steil A, Sirois P. Modulation of allergic and immune complex-induced lung inflammation by bradykinin receptor antagonists. Inflamm Res. 2004;53:78-83 pubmed..The effect of bradykinin (B(1) or B(2)) receptor antagonists was studied in allergic and immune-complex-induced lung inflammation...
- Ma Q, Heavens R. Basal expression of bradykinin B(1) receptor in the spinal cord in humans and rats. Neuroreport. 2001;12:2311-4 pubmed..Immunohistochemical staining demonstrated B(1)-positive neurons in the spinal cord dorsal horn, suggesting that the B(1) receptor is constitutively expressed by spinal neurons. ..
- McLean P, Perretti M, Ahluwalia A. Inducible expression of the kinin B1 receptor in the endotoxemic heart: mechanisms of des-Arg9bradykinin-induced coronary vasodilation. Br J Pharmacol. 1999;128:275-82 pubmed..Additionally, B1 receptor antagonists partially reversed endotoxin-induced hypotension. Therefore activation of B1 receptors may have a role to play in the vascular changes associated with endotoxemia. ..
- Cloutier F, Couture R. Pharmacological characterization of the cardiovascular responses elicited by kinin B(1) and B(2) receptor agonists in the spinal cord of streptozotocin-diabetic rats. Br J Pharmacol. 2000;130:375-85 pubmed..Thus, this study affords an accessible model for studying the expression, the pharmacology and physiopathology of the B(1) receptor in the central nervous system. ..
- Yang X, Polgar P. Genomic structure of the human bradykinin B1 receptor gene and preliminary characterization of its regulatory regions. Biochem Biophys Res Commun. 1996;222:718-25 pubmed..Primer extension analysis mapped the transcriptional initiation site 21 base pairs downstream of a TATA sequence. Two Aluc sequences and two distinct functional promoters were found in the human BK B1 receptor gene. ..
- 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
- Duchene J, Lecomte F, Ahmed S, Cayla C, Pesquero J, Bader M, et al. A novel inflammatory pathway involved in leukocyte recruitment: role for the kinin B1 receptor and the chemokine CXCL5. J Immunol. 2007;179:4849-56 pubmed..This study unveils a proinflammatory pathway centered on kinin B1 receptor activation of CXCL5 leading to leukocyte trafficking and highlights the B1 receptor as a potential target in the therapeutics of inflammatory disease. ..
- 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. ..
- Campos M, Ongali B, De Souza Buck H, Schanstra J, Girolami J, Chabot J, et al. Expression and distribution of kinin B1 receptor in the rat brain and alterations induced by diabetes in the model of streptozotocin. Synapse. 2005;57:29-37 pubmed..This may offer the advantage of reducing putative central side effects with B1 receptor antagonists if used for the treatment of diabetic complications in the periphery. ..
- Noda M, Kariura Y, Amano T, Manago Y, Nishikawa K, Aoki S, et al. Expression and function of bradykinin receptors in microglia. Life Sci. 2003;72:1573-81 pubmed..Our data provide the first evidence that microglia express functional BK receptors and support the idea that microglia play an important role in CNS inflammatory responses. ..
- Wang P, Cenedeze M, Pesquero J, Pacheco Silva A, Camara N. Influence of bradykinin B1 and B2 receptors in the immune response triggered by renal ischemia-reperfusion injury. Int Immunopharmacol. 2006;6:1960-5 pubmed..In conclusion, the absence of B1R had a protective role against inflammatory responses developed after renal ischemia-reperfusion injury. ..
- 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. ..
- Vianna R, Ongali B, Regoli D, Calixto J, Couture R. Up-regulation of kinin B1 receptor in the lung of streptozotocin-diabetic rat: autoradiographic and functional evidence. Br J Pharmacol. 2003;138:13-22 pubmed..The overexpression of B(1) receptors seems to depend on neutrophils influx and appears to be associated with hyperglycaemia. ..
- Rodriguez A, Pereira Flores K, Hernández Salinas R, Boric M, Velarde V. High glucose increases B1-kinin receptor expression and signaling in endothelial cells. Biochem Biophys Res Commun. 2006;345:652-9 pubmed..iNOS protein levels were also increased in high glucose. These results demonstrate the participation of the B1 receptor in the signaling pathways mediated by kinins in high glucose. ..
- Moniwa N, Agata J, Hagiwara M, Ura N, Shimamoto K. The role of bradykinin B1 receptor on cardiac remodeling in stroke-prone spontaneously hypertensive rats (SHR-SP). Biol Chem. 2006;387:203-9 pubmed..These results suggest that the role of B1R in the heart may be attenuation of cardiac remodeling via inhibition of the expression of MAP kinases and TGF-beta1 through an increase in eNOS activity in a hypertensive condition. ..
- McLean P, Picard C, Garcia Villar R, Ducos de Lahitte R, More J, Fioramonti J, et al. Role of kinin B1 and B2 receptors and mast cells in post intestinal infection-induced hypersensitivity to distension. Neurogastroenterol Motil. 1998;10:499-508 pubmed..SR 142801 was inactive in both groups. In conclusion, mast cells and kinin-mediated nociception appear to be involved in post-infection intestinal hypersensitivity whereas tachykinin NK1 and NK3 receptors do not. ..
- Bertram C, Baltic S, Misso N, Bhoola K, Foster P, Thompson P, et al. Expression of kinin B1 and B2 receptors in immature, monocyte-derived dendritic cells and bradykinin-mediated increase in intracellular Ca2+ and cell migration. J Leukoc Biol. 2007;81:1445-54 pubmed..BK, which increases the migration of immature hMo-DC in vitro, may play an important role in the migration of immature DC in noninflammatory conditions and may also be involved in the recruitment of immature DC to sites of inflammation. ..
- DomBourian M, Turner N, Gerovac T, Vemuganti R, Miranpuri G, Tureyen K, et al. B1 and TRPV-1 receptor genes and their relationship to hyperalgesia following spinal cord injury. Spine (Phila Pa 1976). 2006;31:2778-82 pubmed..This finding is consistent with past work regarding the role of these receptors in nociception and indicates that ongoing modifiable processes are occurring in the spinal cord that lead to clinical pain syndromes. ..
- Gabra B, Berthiaume N, Sirois P, Nantel F, Battistini B. The kinin system mediates hyperalgesia through the inducible bradykinin B1 receptor subtype: evidence in various experimental animal models of type 1 and type 2 diabetic neuropathy. Biol Chem. 2006;387:127-43 pubmed..We discuss the efficacy of selective antagonists of the inducible bradykinin B1 receptor (BKB1-R) subtype against hyperalgesia assessed by various nociceptive tests...
- Cao T, Brain S, Khodr B, Khalil Z. B1 and B2 antagonists and bradykinin-induced blood flow in rat skin inflammation. Inflamm Res. 2002;51:295-9 pubmed..The results suggest that the involvement of the inducible B1 receptor in skin inflammation site is related to the site, duration and recurrence of the injury condition. ..
- Lagneux C, Bader M, Pesquero J, Demenge P, Ribuot C. Detrimental implication of B1 receptors in myocardial ischemia: evidence from pharmacological blockade and gene knockout mice. Int Immunopharmacol. 2002;2:815-22 pubmed..This study demonstrates that B1 receptors are induced during myocardial ischemia where they could play a detrimental role in mice. ..
- Gougat J, Ferrari B, Sarran L, Planchenault C, Poncelet M, Maruani J, et al. 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 bradyk. J Pharmacol Exp Ther. 2004;309:661-9 pubmed..o.) prevented neuropathic thermal pain induced by sciatic nerve constriction in the rat. In conclusion, SSR240612 is a new, potent, and orally active specific non-peptide bradykinin B(1) receptor antagonist. ..
- Moreau M, Garbacki N, Molinaro G, Brown N, Marceau F, Adam A. The kallikrein-kinin system: current and future pharmacological targets. J Pharmacol Sci. 2005;99:6-38 pubmed
- Haddad E, Fox A, Rousell J, Burgess G, McIntyre P, Barnes P, et al. Post-transcriptional regulation of bradykinin B1 and B2 receptor gene expression in human lung fibroblasts by tumor necrosis factor-alpha: modulation by dexamethasone. Mol Pharmacol. 2000;57:1123-31 pubmed..Nuclear run-on experiments demonstrate that the induction of B1 and the up-regulation of B2 receptors as well as the inhibitory effect of dexamethasone are entirely mediated through post-transcriptional mechanisms. ..
- Gabra B, Sirois P. Hyperalgesia in non-obese diabetic (NOD) mice: a role for the inducible bradykinin B1 receptor. Eur J Pharmacol. 2005;514:61-7 pubmed..It is suggested that bradykinin B(1) receptor antagonism could become a novel therapeutic approach to the treatment of diabetic neuropathic complications. ..
- Gabra B, Sirois P. Pathways for the bradykinin B1 receptor-mediated diabetic hyperalgesia in mice. Inflamm Res. 2004;53:653-7 pubmedExperimental evidence has shown that the bradykinin B1 receptor (BKB1-R) is involved in the development of hyperalgesia associated with diabetes since specific BKB1-R antagonists significantly inhibited the hyperalgesic activity observed ..
- Li H, Yin H, Yao Y, Shen B, Bader M, Chao L, et al. Tissue kallikrein protects against pressure overload-induced cardiac hypertrophy through kinin B2 receptor and glycogen synthase kinase-3beta activation. Cardiovasc Res. 2007;73:130-42 pubmed
- Sangsree S, Brovkovych V, Minshall R, Skidgel R. Kininase I-type carboxypeptidases enhance nitric oxide production in endothelial cells by generating bradykinin B1 receptor agonists. Am J Physiol Heart Circ Physiol. 2003;284:H1959-68 pubmed..These data show that cellular kininase I-type carboxypeptidases can enhance kinin signaling and NO production by converting B(2) agonists to B(1) agonists, especially in inflammatory conditions. ..
- Ni A, Chai K, Chao L, Chao J. Molecular cloning and expression of rat bradykinin B1 receptor. Biochim Biophys Acta. 1998;1442:177-85 pubmedThe gene encoding rat bradykinin B1 receptor has been cloned by using a partial rat B1 cDNA probe. The rat B1 receptor gene contains two exons and the entire coding region is within the second exon...
- Cayla C, Todiras M, Iliescu R, Saul V, Gross V, Pilz B, et al. Mice deficient for both kinin receptors are normotensive and protected from endotoxin-induced hypotension. FASEB J. 2007;21:1689-98 pubmed..These results clearly demonstrate a pivotal role of kinins and their receptors in hypotension induced by endotoxemia in mice. ..
- Tsukagoshi H, Horie T, Fukabori Y, Shimizu Y, Iwamae S, Hisada T, et al. Regulation by interleukin-1beta of gene expression of bradykinin B1 receptor in MH-S murine alveolar macrophage cell line. Biochem Biophys Res Commun. 1999;259:476-82 pubmedThe effects of recombinant murine interleukin (IL)-1beta on gene expression of murine bradykinin B1 receptor (BDKRB1) in MH-S murine alveolar macrophage cell line were evaluated...
- Ismael M, Talbot S, Carbonneau C, Beausejour C, Couture R. Blockade of sensory abnormalities and kinin B(1) receptor expression by N-acetyl-L-cysteine and ramipril in a rat model of insulin resistance. Eur J Pharmacol. 2008;589:66-72 pubmed publisher..Both therapies were associated with a reduction of the expression of the pro-nociceptive kinin B(1) receptor. ..
- 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. ..
- 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. ..
- Duka I, Kintsurashvili E, Gavras I, Johns C, Bresnahan M, Gavras H. Vasoactive potential of the b(1) bradykinin receptor in normotension and hypertension. Circ Res. 2001;88:275-81 pubmed..Furthermore, they indicate that experimental manipulations to produce hypertension also induce upregulation of the B(1)R, but not the B(2)R, in cardiac and renal tissues. ..
- Lawson S, Gabra B, Nantel F, Battistini B, Sirois P. Effects of a selective bradykinin B1 receptor antagonist on increased plasma extravasation in streptozotocin-induced diabetic rats: distinct vasculopathic profile of major key organs. Eur J Pharmacol. 2005;514:69-78 pubmed
- Lungu C, Dias J, França C, Ongali B, Regoli D, Moldovan F, et al. Involvement of kinin B1 receptor and oxidative stress in sensory abnormalities and arterial hypertension in an experimental rat model of insulin resistance. Neuropeptides. 2007;41:375-87 pubmed..The over expressed B(1)R contributes centrally to arterial hypertension and in the periphery to sensory abnormalities. ..
- Andre E, Gazzieri D, Bardella E, Ferreira J, Mori M, Saul V, et al. Expression and functional pharmacology of the bradykinin B1 receptor in the normal and inflamed human gallbladder. Gut. 2008;57:628-33 pubmed publisher..Bradykinin B(1) receptor has an important role as a spasmogen of human gallbladder, and selective antagonists of the B(1) receptor may represent a valid therapeutic option to control pain in patients with acute cholecystitis. ..
- Yin H, Chao J, Bader M, Chao L. Differential role of kinin B1 and B2 receptors in ischemia-induced apoptosis and ventricular remodeling. Peptides. 2007;28:1383-9 pubmed..These results indicate that the kinin B2 receptor, but not the B1 receptor, protects against I/R-induced cardiac dysfunction by inhibiting apoptosis and limiting ventricular remodeling. ..
- Abdouh M, Khanjari A, Abdelazziz N, Ongali B, Couture R, Hasséssian H. Early upregulation of kinin B1 receptors in retinal microvessels of the streptozotocin-diabetic rat. Br J Pharmacol. 2003;140:33-40 pubmed..These results suggest that kinin receptors may be potential targets for therapeutics to treat retinopathies. ..
- Westermann D, Lettau O, Sobirey M, Riad A, Bader M, Schultheiss H, et al. Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor. Biol Chem. 2008;389:713-8 pubmed publisher..These insights might have useful implications for future studies utilizing B1R antagonists for treatment of human DOX cardiomyopathy. ..
- Ma Q. The expression of bradykinin B(1) receptors on primary sensory neurones that give rise to small caliber sciatic nerve fibres in rats. Neuroscience. 2001;107:665-73 pubmed..Since peripheral nociceptive information is primarily transmitted by C- and A(delta)-fibres, B(1) receptors may be involved in the modulation of nociceptive transduction or transmission. ..
- Duka I, Duka A, Kintsurashvili E, Johns C, Gavras I, Gavras H. Mechanisms mediating the vasoactive effects of the B1 receptors of bradykinin. Hypertension. 2003;42:1021-5 pubmed..The data confirm that the B1R becomes markedly expressed in the absence of B2R and suggest that it contributes to vasodilation by inhibiting a vasoconstricting product of the arachidonic acid cascade acting via the PGH2/TxA2 receptor. ..
- Gabra B, Benrezzak O, Pheng L, Duta D, Daull P, Sirois P, et al. Inhibition of type 1 diabetic hyperalgesia in streptozotocin-induced Wistar versus spontaneous gene-prone BB/Worchester rats: efficacy of a selective bradykinin B1 receptor antagonist. J Neuropathol Exp Neurol. 2005;64:782-9 pubmed..Thus, selective antagonism of the inducible BKB1-R subtype may constitute a novel and potential therapeutic approach for the treatment of PDN. ..
- Ifuku M, Färber K, Okuno Y, Yamakawa Y, Miyamoto T, Nolte C, et al. Bradykinin-induced microglial migration mediated by B1-bradykinin receptors depends on Ca2+ influx via reverse-mode activity of the Na+/Ca2+ exchanger. J Neurosci. 2007;27:13065-73 pubmed..These observations support the view that BK functions as a chemoattractant by using the distinct signal pathways in the brain and, thus, attracts microglia to the lesion site in vivo. ..
- Gabra B, Merino V, Bader M, Pesquero J, Sirois P. Absence of diabetic hyperalgesia in bradykinin B1 receptor-knockout mice. Regul Pept. 2005;127:245-8 pubmed..Taken together, the results confirm the crucial role of the BKB1-R, upregulated alongside inflammatory diabetes, in the development of diabetes-induced hyperalgesia. ..