Disease relevance of Bdkrb2

• Regulation of cardiac bradykinin B1- and B2-receptor mRNA in experimental ischemic, diabetic, and pressure-overload-induced cardiomyopathy [1].
• These results demonstrate that brain injury-mediated bradykinin production induces vasogenic brain edema by B2 receptor stimulation [2].
• Down-regulation of bradykinin B2-receptor mRNA in the heart in pressure-overload cardiac hypertrophy in the rat [3].
• 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 development of brain edema [4].
• CONCLUSIONS: Our findings provide further support for a mediator role of bradykinin in ischemic brain damage including edema formation, obviously by ligand binding to the bradykinin B2 receptor [4].

Psychiatry related information on Bdkrb2

• The two analogues alone and the fragment BK-(1-8), a potent stimulant of B1-receptors for BK, failed to alter reaction time and only the B2-receptor antagonist reduced BK-induced behavioural responses [5].

High impact information on Bdkrb2

• Two months after MI, rats were treated for 2 mo with: (a) vehicle; (b) the ACEi ramipril, with and without the B2 receptor antagonist icatibant (B2-ant); or (c) an AT1-ant with and without an AT2-antagonist (AT2-ant) or B2-ant [6].
• MBP and poly-L-lysine induced an increase in airway responsiveness, which was inhibited by pretreatment with a selective BK-2 receptor antagonist, NPC 17713 (250 micrograms/ml) [7].
• [Thi5,8,DPhe7]bradykinin, where Thi is beta-(2-thienyl)-alanine, is a very weak partial agonist and inhibits the bradykinin-mediated ion flux, suggesting the cDNA encodes a smooth muscle, rather than a neuronal, B2 receptor subtype [8].
• In competitive binding assays, unlabeled BK, Hoe 140 (a specific BK B2 receptor antagonist), and des-Arg9,[Leu8]BK (a BK B1 receptor antagonist) displaced [125I-Tyr8]BK with an IC50 of 4.3, 0.041, and 307 nmol/L, respectively [9].
• Homodimers of an amino-terminal extended BK analog and a V1a-selective antagonist represent the first examples of new classes of B2 BKR and V1a VPR antagonists, respectively [10].

Chemical compound and disease context of Bdkrb2

• LPS-induced hyperalgesia was reversed by the B2 receptor antagonist, HOE 140 (10--30 pmol), when administered i.c.v. but not systemically (0.01--1 mmol/kg, i.v.). Central co-administration of the B1 receptor antagonists, des-Arg9-Leu8 Bk (0.1--1 nmol) or des-Arg10 HOE 140 (0.1--1 nmol) had no effect on thermal or mechanical hyperalgesia [11].
• 1. The effect of central injection of selective kinin B1 and B2 receptor antagonists on the febrile response induced by endotoxin (E. coli lipopolysaccharide, LPS) in rats was investigated [12].
• Kinin B2 receptor is not involved in enalapril-induced apoptosis and regression of hypertrophy in spontaneously hypertensive rat aorta: possible role of B1 receptor [13].
• The kinin B1 receptor antagonists [Leu8]des-Arg9-BK (3-30 nmol/kg) and R-715 (100 nmol/kg), the B2 receptor antagonists Hoe 140 (15 nmol/kg) and LF 16.0687 (3 and 10 mg/kg), as well as the NSAID diclofenac sodium (1 and 3 mg/kg) significantly reversed zymosan-induced hyperalgesia [14].
• METHODS: To assess a potential role of bradykinin, subtotally nephrectomized Sprague-Dawley rats (SNX) received either the ACE inhibitor Ramipril (Rami, 0.2 mg/kg body weight p.o.), the specific B2 bradykinin receptor antagonist Hoe140 (0.2 mg/kg body weight, s.c.), or a combination of both, and were compared to sham-operated controls [15].

Biological context of Bdkrb2

• The effects of angiotensin II on cell differentiation and cyclic GMP production were mediated via the AT2 receptor and further enhanced by bradykinin B2 receptor blockade [16].
• The results indicate that both B1R and B2R contribute to the maintenance of normal BP, but one can compensate for inhibition of the other, and the chronic inhibition of both leads to significant upregulation in the genes of related vasoactive systems [17].
• ERK 1 and 2 phosphorylation and expression of B1R and B2R were assessed by Western blot analysis [18].
• The interplay of P1 and P2 may be important in the regulation of bradykinin B2 receptor gene expression in response to inflammatory stress and during development [19].
• Reverse transcription-polymerase chain reaction analysis detected two different bradykinin B2 receptor mRNAs containing or lacking exon 3 in all rat tissues tested, providing evidence for alternative splicing of the 5'-untranslated sequence [20].

Anatomical context of Bdkrb2

• B2R immunoreactivity was localized throughout the bladder, including the urothelium and detrusor smooth muscle [21].
• B2 bradykinin receptor mediates the stimulatory effect of bradykinin on rat germ cell proliferation in vitro [22].
• The increased endothelial cell proliferation that was observed 24 h after intra-articular injection of substance P (10 nmols) was completely blocked by either NK1 or B2 receptor antagonists (SR140333 or FR172357, respectively) [23].
• B2R antagonism decreased leukocyte and synovial CD44 and CD54 and endothelial CD11b expression [24].
• Purification and characterisation of B2 bradykinin receptor from rat uterus [25].

Associations of Bdkrb2 with chemical compounds

• In contrast, B2 receptor blockade had no effect or even increased these angiotensin II effects [16].
• Only combined administration of B1R and B2R antagonists produced a significant BP increase from a baseline of 107-119 mmHg at end point, which could be partly prevented by losartan and was not associated with change in catecholamines, suggesting no involvement of the sympathoadrenal system [17].
• The biochemical properties of the solubilised B2 BK receptor correspond to those of a hydrophobic acidic glycoprotein (isoelectric focusing gave a value of 4.5-4.7) that binds specifically to wheat germ agglutinin but has no affinity for either concanavalin A or lentil lectin, suggesting the absence of terminal mannose or glucose residues [25].
• The B2 bradykinin receptor antagonist HOE 140 and the B1 bradykinin receptor antagonist des-Arg9[Leu8]bradykinin displaced the binding of [3H]bradykinin from dog membranes with IC50 values of 0.38 and 217.3 nmol/l, respectively, suggesting that bradykinin binds to a B2-type receptor [26].
• In competitive experiments using membranes prepared from Chinese hamster ovary cells expressing the human bradykinin receptor subtypes, FR190997 showed a high affinity binding to the B2 receptor with IC50 value of 5.3 nM and no binding affinity for the B1 receptor [27].

Regulatory relationships of Bdkrb2

• Superfusion with Bk (10 nM) increased [Ca++]i by 96 +/- 10 nM over basal levels in approximately 80% of the neurons tested that were not affected by a Bk-1 receptor antagonist but were inhibited 72% by a Bk-2 receptor antagonist [28].
• We investigated whether endogenous kinin levels are subject to short-loop-feedback regulation mediated by the B2 receptor and whether endogenous kinins acting through the B2 receptor influence plasma renin levels and circulating and tissue angiotensin peptide levels [29].
• The B2 receptor antagonists had no significant inhibitory effects on kallidin-stimulated phosphoinositide metabolism or prolactin release [30].

Other interactions of Bdkrb2

• Our findings indicate that the bradykinin 2 receptor (B2R) but not the bradykinin 1 receptor (B1R) is expressed in control bladder urothelium [21].
• Synovitis-enhanced endothelial cell proliferation was also inhibited by the B2 receptor antagonist alone (27%) but not by the NK1 receptor antagonist alone [23].
• The nonselective cyclooxygenase (COX) inhibitors S-(-)-ketoprofen (10 microM) and piroxicam (30 microM) markedly depressed the concentration-response curves to [desArg9]-BK and [Hyp3, Tyr(Me)8]-BK in control bladders, but neither drug affected the B1 or B2 receptor agonist-mediated responses in inflamed bladders [31].
• HOE 140, a BK2 receptor antagonist (0.01, 0.1, and 1 nmol/L), prevented the stimulatory effect of BK on glucagon secretion in a concentration-dependent manner [32].
• CONCLUSIONS: A new inhibitory pathway of the early steps of IGF-I signaling by the B2 receptor is found both in cultured MCs and in IG, which involves a calcium-dependent tyrosine phosphatase activity [33].

Analytical, diagnostic and therapeutic context of Bdkrb2

• Using real-time PCR, we found that B1R mRNA expression increased 2.9-fold in hearts of older rats (24 mo of age) compared with younger rats (3 mo of age), whereas B2R gene expression remained unchanged [34].
• In mature testis, in situ hybridization and immunohistochemistry localized B2R mRNA and protein besides endothelial cells of blood vessels exclusively on pachytene spermatocytes and round and elongated spermatids [35].
• Molecular cloning and sequence analysis of rat bradykinin B2 receptor gene [36].
• We conclude that early activation of B2R augmented ROS generation in ischemia/reperfusion renal injury, resulting in subsequent apoptosis, inflammation, and tissue damage [37].
• METHODS: Using a RT-PCR/Southern blot approach allowing relative quantification of mRNA levels, ten different microdissected rat nephron segments were analyzed for the presence of the B1- and B2-receptor before and after endotoxin treatment to induce experimental inflammation [38].

References