Disease relevance of Bdkrb2

• OBJECTIVE: We assessed the role of glycogen synthase kinase-3beta (GSK-3beta) and kinin B2 receptor in mediating tissue kallikrein's protective effects against cardiac hypertrophy [1].
• The protective role of kinin B2 receptor in cardiac hypertrophy was further confirmed in kinin receptor knockout mice as heart weight/body weight ratio and cardiomyocyte size increased significantly in kinin B2 receptor knockout mice after AC compared to wild type and B1 receptor knockout mice [1].
• The potent non-peptide B2 receptor (R) antagonist, Anatibant mesylate (Ms) (LF 16-0687 Ms), reduces brain edema and improves neurological function recovery in various focal and diffuse models of traumatic brain injury in rodents [2].
• Autoradiographic analysis of mouse brain kinin B1 and B2 receptors after closed head trauma and ability of Anatibant mesylate to cross the blood-brain barrier [2].
• Thus TK and the B2 receptor play a critical role in the cardioprotection afforded by two experimental maneuvers of potential clinical relevance, IPC and ACE inhibition, during ischemia [3].

Psychiatry related information on Bdkrb2

• Studies in knockout mice indicated that the central effect of Ang II on alcohol consumption is mediated by the angiotensin receptor AT1 whereas the AT2 receptor and the bradykinin B2 receptor are not involved [4].

High impact information on Bdkrb2

• Three polypeptide chains, A, B1, and B2, have been described for mouse laminin, a basement membrane protein [5].
• Induction of kidney mesenchyme differentiation in vitro led to an increased expression of B1 and B2 chain mRNA on day 1 of development [5].
• Nuclear run-on experiments show that the down-regulation of B2 genes during F9 embryonal carcinoma cell differentiation into endoderm occurs at the transcriptional level and that other class III genes, including those encoding tRNA, show a similar response [6].
• HSDM1C1 cells possess a B2 bradykinin receptor, a type more sensitive to native bradykinin than to related peptides, including Met-Lys- and desArg9-bradykinin [7].
• Regulation of prostaglandin synthesis mediated by thrombin and B2 bradykinin receptors in a fibrosarcoma cell line [7].

Chemical compound and disease context of Bdkrb2

• The nociceptive response to intraplantar injection of bradykinin (10 nmol) and hyperalgesia induced by carrageenan (0.6 mg) were absent in Bk2r-/- mice, indicating that stimulation of B2 receptors is an essential step in the initiation of some nociceptive and inflammatory reactions [8].
• The kinin B1 receptor antagonist [Leu8]des-Arg9-bradykinin or the B2 antagonist d-Arg[Hyp3,Thi5,D-Tic7, Oic8]bradykinin (HOE-140) was injected subcutaneously into STZ mice at 300 micrograms/kg body weight twice a day and 500 micrograms/kg per day, respectively [9].
• The i.p.l. co-injection of tyrosine8-bradykinin (a B2 agonist, 3-15 nmol/paw) with formalin (0.01 or 0.5%) potentiated the pain response and paw oedema in BCG and saline-pre-treated animals to the same extent (P < 0.01) [10].
• Thus, in mice, kinins acting via B2 receptors do not participate in (1) maintenance of normal basal blood pressure, (2) establishment and maintenance of hypertension induced by DOCA-salt or aortic coarctation, and (3) chronic antihypertensive and cardiac antihypertrophic effects of ACEi in DOCA-salt and aortic coarctation hypertension [11].
• 5. These results suggest that BK1 along with BK2 receptors are located on capsaicin-sensitive fibres, where they may modulate the degree of neurogenic inflammation [12].

Biological context of Bdkrb2

• Anatibant Ms (Ki = 22 pM) displaced the B2R radioligand from its binding sites in several areas of the forebrain, basal ganglia and hindbrain [2].
• Taken together, these results indicate that under basal conditions, the kinin B2 receptor is not an important determinant of blood pressure in mice but is involved in the control of regional vascular tone in the coronaries and the kidneys [13].
• In B2-/-, B1 receptor gene expression was constitutively high [3].
• Cardiovascular phenotypes of kinin B2 receptor- and tissue kallikrein-deficient mice [13].
• However, heart rate was lower in B2-/- mice compared with TK-/- and WT mice [13].

Anatomical context of Bdkrb2

• Evans blue extravasation in brain tissue at 4 h after CHT was abolished by Anatibant Ms. It appeared that Anatibant Ms penetrated into the brain in sufficient amounts, particularly after disruption of the blood-brain barrier, to account for its B2R-mediated neuro- and vascular protective effects [2].
• The results suggest that the mouse B2 BK receptor couples to phospholipase C in CHO cells and that its activation results in biphasic [Ca2+]i increases, by mobilization of intracellular Ca2+ and store-depletion-mediated Ca2+ influx, the latter of which is tyrosine phosphorylation dependent [14].
• EP24.15 was also co-immunoprecipitated with AT1 and B2 in rat kidney brush border membranes (BBM) and basolateral membranes (BLM) [15].
• During normal salt intake, renal interstitial fluid NO and cGMP levels in B2-null mice were not different from those of wild-type mice [16].
• [3H]bradykinin receptor-binding, receptor-recycling, and receptor-internalization of the B2 bradykinin receptor in the murine osteoblast-like cell line MC3T3-E1 [17].

Associations of Bdkrb2 with chemical compounds

• The B1 receptor is a heptahelical receptor distinct from the B2 receptor in that it is highly inducible by inflammatory mediators such as bacterial lipopolysaccharide and interleukins [18].
• TAp73 also activated the bradykinin B2 receptor (B2R) promoter, a developmentally regulated gene involved in regulation of sodium excretion [19].
• OBJECTIVE: Previous studies have suggested that activation of angiotensin II (ANG II) type 2 (AT2) receptors results in nitric oxide (NO) release via activation of endothelial bradykinin B2 (B2R) receptors [20].
• Ca2+ release and Ca2+ influx in Chinese hamster ovary cells expressing the cloned mouse B2 bradykinin receptor: tyrosine kinase inhibitor-sensitive and- insensitive processes [14].
• PD123319 decreased NO and cGMP in both wild-type and B2-null mice [16].

Regulatory relationships of Bdkrb2

• Angiotensin AT2 receptors directly stimulate renal nitric oxide in bradykinin B2-receptor-null mice [16].
• Bradykinin B2 receptor activates extracellular signal-regulated protein kinase in mIMCD-3 cells via epidermal growth factor receptor transactivation [21].
• 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 [22].
• OBJECTIVE: To investigate the effects of glucocorticoids on the TNF-alpha up-regulated bradykinin B1 and B2 receptor response [23].
• 5. The mechanism by which B2 receptor agonists inhibit LPS-induced eosinophil accumulation was investigated by pretreating the animals with indomethacin or a selective cyclooxygenase-2 inhibitor, NS-398 [24].

Other interactions of Bdkrb2

• In WT and TK-/- mice, both B2 and B1 mRNA levels increased several fold during IR, and even more during IPC+IR [3].
• Blockade of the AT1 receptor enhances the production of NO via the AT2 receptor in both wild-type and B2-null mice [16].
• The transcriptional effects of TAp73 on AQP-2 and B2R were independent of p53 [19].
• The B2 receptor is constitutively expressed, and its targeted disruption leads to salt-sensitive hypertension and altered nociception [18].
• BK-induced contractions were prevented by mergetpa (a carboxypeptidase M inhibitor) (10 microM) and by a the B receptor antagonist, AcLys[DbetaNal7,Ile8]desArg9BK (R 715) (0.88 microM), while not being influenced by the B2 receptor antagonist HOE 140 (0.38 microM) [25].

Analytical, diagnostic and therapeutic context of Bdkrb2

• METHODS: We investigated the effect and mechanisms of tissue kallikrein using hypertrophic animal models of rats as well as mice deficient in kinin B1 or B2 receptor after aortic constriction (AC) [1].
• Our results indicate that during ingestion of a low-salt diet, production of NO is mediated mainly via the AT2-B2 receptor cascade [16].
• Using quantitative RT-PCR analysis of B1 and B2 mRNAs expression, we described for the first time a correlation between the kallikrein-kinin system (KKS) and severe obesity in mice [26].
• In a first step to better understand how BK and its receptors could be involved in such a large variety of biological effects, we used microarray analysis to identify, under physiological conditions, the global renal gene expression profile in mice lacking either the kinin B1 or B2 receptor [27].
• In two separate groups of wild type hearts, B1 and B2 receptors were blocked with 3 nM of (des-Arg9, Leu8)-bradykinin and 10 nM of Hoe 140, respectively, (started 15 min before ischemia and stopped before the reperfusion) [28].

References