Disease relevance of Bdkrb1

• 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 [1].
• These findings support other evidence for an involvement of B1 receptors in inflammatory hyperalgesia and suggest that B1 receptor antagonists may be clinically useful as anti-inflammatory and analgesic drugs [2].
• Systemic treatment with Mycobacterium bovis bacillus Calmette-Guérin (BCG) potentiates kinin B1 receptor agonist-induced nociception and oedema formation in the formalin test in mice [3].
• These data show that the long-term systemic treatment of mice with BCG produced dose-related potentiation of B1 receptor agonist-mediated nociception and oedema formation, without affecting similar responses caused by the B2 receptor agonist tyrosine8-bradykinin [3].
• 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 [4].

High impact information on Bdkrb1

• The stimulatory effect of TK was mimicked by bradykinin (BK) and could be reversed by application of JE049, a BK receptor type 2 antagonist [5].
• 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 [6].
• Thus, the kinin B1 receptor plays an essential physiological role in the initiation of inflammatory responses and the modulation of spinal cord plasticity that underlies the central component of pain [6].
• Using whole-cell patch-clamp recordings, we show that the B1 receptor was not necessary for regulating the noxious heat sensitivity of isolated nociceptors [6].
• No atypic high-affinity binding sites for the B1 receptor agonist des-Arg9-BK could be observed [7].

Chemical compound and disease context of Bdkrb1

• The contributions of B1 and B2 bradykinin receptors to acute and chronic inflammatory hyperalgesia were examined using the peptide B1 receptor antagonist des-Arg9[Leu8]bradykinin and transgenic Bk2r-/- mice [2].

Biological context of Bdkrb1

• Analysis of B1R gene expression by reverse transcription-polymerase chain reaction (PCR) in cardiac and renal tissues revealed marked expression at baseline, with further upregulation by 1.5- to 2-fold after various manipulations [8].
• The B1R antagonist produced significant (P<0.05) blood pressure increases of 17.7+/-3.1 mm Hg in group 1 and 10.4+/-3 mm Hg in group 3, whereas their vehicle-treated respective control groups 2 and 4 had no significant blood pressure changes [8].
• 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 [8].
• Renal gene expression profiling using kinin B1 and B2 receptor knockout mice reveals comparable modulation of functionally related genes [9].
• STZ mice treated with the B1 receptor antagonist showed normal glycemia and complete normalization of diuresis and protein, nitrite, and kallikrein excretion [4].

Anatomical context of Bdkrb1

• Whereas B1R is barely detected in most brain regions, B2R is extensively distributed, displaying the highest densities in the hindbrain [1].
• The contraction induced by desArg9BK had a longer duration than that evoked by BK and increased during incubation in vitro in stomachs of wild-type controls, while in the transgenic B2 receptor knockout mice, the contractions evoked by desArg9BK and BK were similar and followed the B1 receptor agonist pattern [10].
• Taken together, these data suggest a deleterious effect for kinin B1 receptor and a protective effect for kinin B2 receptor during the development of the temporal lobe epilepsy [11].
• In this report, we describe oocyte expression experiments showing that the B1 receptor in WI38 human fibroblast cells is encoded by a distinct mRNA approximately 2 kb shorter than that encoding the B2 receptor [12].
• Evidence for in vitro expression of B1 receptor in the mouse trachea and urinary bladder [13].

Associations of Bdkrb1 with chemical compounds

• Bradykinin normally exerts its vasodilatory effect via the B2 receptor (B2R), but in this receptor's absence, the B1 receptor becomes expressed and activated [8].
• Injection with the B1R agonist produced a hypotensive response (12+/-1.3 mm Hg), which was further accentuated by TxA2 blockade (21.7+/-4.1 mm Hg) [8].
• Role of kinin B1 and B2 receptors in the development of pilocarpine model of epilepsy [11].
• Bk-induced prostaglandin synthesis in isolated osteoblast-like cells and in MC3T3-E1 cells was inhibited by D-Arg0[Hyp3,Thi5,8,D-Phe7]-Bk, whereas the B1 Bk receptor antagonist des-Arg9-Leu8-Bk had no effect [14].
• The B2 Bk receptor agonists Bk and Lys-Bk, but not the B1 Bk receptor agonist des-Arg9-Bk, caused a rapid burst (5 minutes) of prostaglandin E2 and prostacyclin formation in isolated osteoblast-like cells from neonatal mouse calvarial bones and in the murine osteoblastic cell lineage MC3T3-E1 [14].

Regulatory relationships of Bdkrb1

• We conclude that GDNF and neurturin potently upregulate functional B1 receptor expression in small non-peptidergic nociceptive neurones [15].

Other interactions of Bdkrb1

• Expression of the TxA2 receptor gene in renal tissue by quantitative real-time PCR was significantly lower in mice treated with the B1R antagonist, consistent with increased levels of agonist for this receptor [8].
• B 1 receptor transcription activation in response to LPS was abolished by cotransfection with IkappaBalphaDeltaN, an NF-kappaB repressor [16].
• These results suggest that in single NG108-15 cells, EK induces Ca2+ mobilization which is assisted by cross-talk between the EK and BK receptor systems via a pertussis toxin-sensitive G protein [17].

Analytical, diagnostic and therapeutic context of Bdkrb1

• 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 [9].
• Finally, a RT-PCR technique showed an activation of kinin B1 receptor gene transcription, in wild type hearts, subjected to the ischemia-reperfusion sequence [18].
• No change in urinary Ca excretion was observed in B2-/- mice, even after treatment with a kinin B1-receptor antagonist, and these mice adapted normally to the LCa diet [19].
• 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) [20].
• 4. Northern blot hybridization with a specific cDNA probe against mouse B1 receptor mRNA using total RNA extracted from tracheae and urinary bladders freshly removed from Swiss and Bk2r(-/-) mice revealed minimal expression [13].

References