Disease relevance of Bdkrb1

• In contrast, B1R mRNA was not detected in control rat urinary bladder; however, following acute (24 h) and chronic (8 day) CYP-induced cystitis in the rat, B1R mRNA was detected throughout the bladder [1].
• The administration of B1 R antagonist resulted in renal interstitial and glomerular fibrosis in SHR-SP [2].
• Since ERK 1 and 2 phosphorylation is an early event in the induction of matrix secretion and hyperproliferation associated with diabetic nephropathy, activation of B1R and B2R appears to be a useful pharmacological target in the management of this pathology [3].
• Up-regulation of both BK-receptor (BKR) types in early stages of cardiac wound healing induced by ischemia and in chronic stages of cardiac remodeling induced by pressure-overload or by hyperglycemia indicates that kinins play a major role in the complex processes of cardiac tissue injury and repair [4].
• Therefore we have examined B1 bradykinin receptor regulation in rat dorsal root ganglia in a model of inflammatory hyperalgesia, and correlated it with hyperalgesic behaviour [5].

High impact information on Bdkrb1

• 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 [6].
• Single-chain peptides combining AVP and BK directly, AVP(1-9)-BK(1-9) or via a flexible aminohexanoic acid (epsilonAhx) linker, AVP(1-9)-epsilonAhx-BK(1-9), bind with relatively high affinity to the bovine kidney medulla B2a bradykinin receptor (B2a BKR) [7].
• Further development, combining the sequences of receptor subtype-selective antagonists, produced high-affinity chimeric antagonists of the V1a vasopressin receptor (V1a VPR) and the B2a BKR [7].
• [Des-Arg10]-kallidin, a B1 receptor agonist, at concentrations of up to 10(-4) M did not induce any significant increase in CGRP outflow from the rat trachea [8].
• Kinin B1 receptor up-regulation after lipopolysaccharide administration: role of proinflammatory cytokines and neutrophil influx [9].

Chemical compound and disease context of Bdkrb1

• 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 [10].
• These results suggest that in the setting of inflammation, bradykinin hyperalgesia was mediated by both B1 and B2 receptors, and that des-Arg9-bradykinin hyperalgesia was mediated by the B1 receptor [11].
• However, LPS hyperthermia was significantly reduced by systemic administration of indomethacin (1 mumol kg-1, i.v.). 4. Co-administration of the selective B1 receptor antagonists, [des-Arg9, Leu8]BK (0.1 - 1 nmol, i.c.v.) or [des-Arg10] Hoe 140 (0.1 - 1 nmol, i.c.v.), did not prevent LPS-induced hyperthermia [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].

Biological context of Bdkrb1

• Assignment of the kinin receptor B1 and B2 genes (Bdkrb1 and Bdkrb2) to rat chromosome 6q3.2 by FISH and radiation hybrid mapping [15].
• 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 [16].
• The infusion of B1 R antagonist for 4 weeks resulted in a significant elevation of blood pressure and urinary albumin excretion and a decrease in urinary NOx excretion in SHR-SP [2].
• ERK 1 and 2 phosphorylation and expression of B1R and B2R were assessed by Western blot analysis [3].
• B1R signaling suggests involvement in down-regulation of leukocyte activation, transmigration, and homing [17].

Anatomical context of Bdkrb1

• Our findings indicate that the bradykinin 2 receptor (B2R) but not the bradykinin 1 receptor (B1R) is expressed in control bladder urothelium [1].
• The occurrence of kinin-B1 receptor binding sites on acinar cell membranes was demonstrated by micro-autoradiography [18].
• We have investigated the motor effects of i.v. or topical (onto the bladder serosa) administration of the selective kinin B1 receptor agonist [des-Arg9]-bradykinin ([des-Arg9]-BK) in the normal or inflamed (cyclophosphamide-induced) urinary bladder in urethane-anaesthetized rats [19].
• In an acute model with two hours of ischaemia/two hours of reperfusion, application of the kinin-B1 receptor antagonist (CP-0298) alone, or in combination with kinin-B2 receptor antagonist (CP-0597), significantly reduced the number of adherent leukocytes in post-capillary venules [18].
• The present study attempted to determine some of the mechanisms underlying B1R upregulation following tissue injury in rat portal vein [20].

Associations of Bdkrb1 with chemical compounds

• Functional B1Rs were demonstrated by evoking ATP release and increases in [Ca(2+)](i) in CYP (24 h)-treated cultured rat urothelial cells with a selective B1 receptor agonist (des-Arg(9)-bradykinin) [1].
• 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 [16].
• Thus, the B1 receptor does not play a regulatory role in either the healthy or in STZ-diabetic heart [21].
• Renal protective role of bradykinin B1 receptor in stroke-prone spontaneously hypertensive rats [2].
• The partially purified BK receptor, enriched 1,500-fold, was then cross-linked to 125I-Tyr0-BK using disuccinimidyl suberate and purified to homogeneity as a single protein species on two-dimensional gel electrophoresis with a molecular mass of 81 kDa [22].

Physical interactions of Bdkrb1

• The BK-receptor complex was not affected by angiotensin II or by arginine vasopressin and atrial natriuretic factor [23].

Regulatory relationships of Bdkrb1

• 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 [24].
• In this study, we evaluated whether p42/p44 mitogen activated protein (MAP) and p38 stress activated protein (SAP) kinases were implicated in the activation of the gene encoding for the B1 receptor after heat stress in rat vascular smooth muscle cells (SMCs) [25].
• Herein, we analyse the role of TNF-alpha and IL-1beta production for PAF-induced B1 receptor upregulation in the rat paw [26].

Other interactions of Bdkrb1

• Bradykinin B1 receptor expression induced by tissue damage in the rat portal vein: a critical role for mitogen-activated protein kinase and nuclear factor-kappaB signaling pathways [20].
• The selective inhibitor of the inducible COX-2 isoenzyme, NS-398 (1 microM), did not inhibit the contractile responses to [desArg9]-BK and [Hyp3, Tyr(Me)8]-BK in either control or inflamed bladders, whereas it significantly potentiated the response to the B1 receptor agonist in inflamed bladders [27].
• The B1 receptor antagonist had no influence on functional renal parameters.CONCLUSIONS: The present study demonstrates an age-dependent activation of the renal KKS in rats with polycystic kidney disease [28].
• Sar4-[d-Phe8]des-Arg9-BK, a B1-receptor agonist that is not degraded by kininase II, also prolonged APD [29].
• RT-PCR and Western blotting analysis showed that BK induced the expression of cPLA2 mRNA and protein, which was inhibited by Hoe140, suggesting the involvement of B2 BK receptors, confirmed by immunofluorescence staining using anti-B2 BK receptor antibody [30].

Analytical, diagnostic and therapeutic context of Bdkrb1

• Immunohistochemistry revealed a B1R protein in the renal tubules and glomeruli in SHR-SP [2].
• 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 [31].
• In kinin-receptor binding studies kinin-B1 receptor showed a 22-fold increase in expression during the time of ischaemia/reperfusion [18].
• Molecular cloning and expression of rat bradykinin B1 receptor [32].
• We detected the expression of inducible bradykinin (BK) B1 receptor mRNA in the rat ileum by the reverse transcriptase-polymerase chain reaction (RT-PCR) method, when the isolated ileum was suspended for at least 1 hr in an aerated Tyrode's solution at 37 degrees [33].

References