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Julie Chao - One of the best experts on this subject based on the ideXlab platform.
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early activation of Bradykinin B2 Receptor aggravates reactive oxygen species generation and renal damage in ischemia reperfusion injury
Free Radical Biology and Medicine, 2006Co-Authors: Wenchih Chiang, Julie Chao, Chiang Ting Chien, Wanwan Lin, Shueiliong Lin, Yungming Chen, Chunfu Lai, Tunjun TsaiAbstract:The kallikrein/kinin system is beneficial in ischemia/reperfusion injury in heart, controversial in brain, but detrimental in lung, liver, and intestine. We examined the role of the kallikrein/kinin system in acute ischemia/reperfusion renal injury induced by 40 min occlusion of the renal artery followed by reperfusion. Rats were infused with tissue kallikrein protein 5 days before (pretreated group) or after (treated group) ischemia. Two days later, the pretreated group exhibited the worst renal dysfunction, followed by the treated group, then the control group. Kallikrein increased tubular necrosis and inflammatory cell infiltration with generation of more tumor necrosis factor-alpha and monocyte chemoattractant protein-1. Reactive oxygen species (ROS), malondialdehyde, and reduced/oxidized glutathione measurement revealed that the oxidative stress was augmented by kallikrein administration in both ischemic and reperfusion phases. The groups with more ROS generation also had more apoptotic renal cells. The deleterious effects of kallikrein on ischemia/reperfusion injury were reversed by cotreatment with Bradykinin B2 Receptor (B2R) antagonist, but not B1 Receptor antagonist, and were not associated with hemodynamic changes. We conclude that early activation of B2R augmented ROS generation in ischemia/reperfusion renal injury, resulting in subsequent apoptosis, inflammation, and tissue damage. This finding suggests the potential application of B2R antagonists in acute ischemic renal disease associated with Bradykinin activation.
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Hypotension in Transgenic Mice Overexpressing Human Bradykinin B2 Receptor
Hypertension, 1997Co-Authors: Dan Zhao Wang, Lee Chao, Julie ChaoAbstract:Bradykinin binds to its Receptor at target organs and exerts a wide spectrum of biological activities including vasodilation, smooth muscle contraction and relaxation, pain, and inflammation. To gain a better insight into the physiological function of this potent vasoactive peptide, we created transgenic mice that harbor the human Bradykinin B2 Receptor transgene under the control of the Rous sarcoma virus 3'-LTR promoter (RSV-cHBKR). Expression of HBKR in these transgenic mice was identified in the aorta, brain, heart, lung, liver, kidney, uterus, and prostate gland by reverse transcription-polymerase chain reaction Southern blot analysis. Two transgenic mouse lines expressing the human B2 Receptor resulted in a significant reduction of blood pressure (84.2 +/- 0.6 mm Hg, n = 28; 76.9 +/- 0.8 mm Hg, n = 24; P < .001) compared with the control littermates (96.9 +/- 0.4 mm Hg, n = 52). Administration of Hoe 140, a Bradykinin B2 Receptor antagonist, restored the blood pressure of the transgenic mice to normal levels within 1 hour, and the effect diminished within 4 hours. The transgenic mice displayed enhanced blood pressure-lowering effect induced by a bolus intra-aortic injection of kinin and showed increased response in kinin-induced uterine smooth muscle contractility compared with control littermates. These studies show that overexpression of human Bradykinin B2 Receptor causes a sustained reduction of blood pressure in transgenic mice. They also suggest that the B2 Receptor-mediated signal transduction pathway plays a role in blood pressure regulation.
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Molecular cloning and sequence analysis of rat Bradykinin B2 Receptor gene.
Biochimica et biophysica acta, 1994Co-Authors: Dan Zhao Wang, Jian Xing, Lee Chao, Julie ChaoAbstract:Abstract The Bradykinin B2 Receptor mediates the effect of kinin. In order to understand the structure and regulation of its expression, we have cloned and sequenced the gene encoding the rat Bradykinin B2 Receptor and its 5′ flanking region from a rat genomic library. The B2 Receptor gene spans 7.3 kb in length and contains three exons which are separated by two introns. It encodes a peptide of 366 amino acids. The transcription initiation site was mapped by the primer extension assay. A variant TATA box sequence, an IL-6 response element and a cAMP response element were identified in the 5′ flanking region of the rat Bradykinin B2 Receptor gene.
C. Shaw - One of the best experts on this subject based on the ideXlab platform.
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ranakinestatin ppf from the skin secretion of the fukien gold striped pond frog pelophylax plancyi fukienensis a prototype of a novel class of Bradykinin B2 Receptor antagonist peptide from ranid frogs
The Scientific World Journal, 2014Co-Authors: Lilin Ge, Jinao Duan, Yingqi Zhang, Mei Zhou, Tianbao Chen, Lei Wang, C. ShawAbstract:The defensive skin secretions of many amphibians are a rich source of Bradykinins and Bradykinin-related peptides (BRPs). Members of this peptide group are also common components of reptile and arthropod venoms due to their multiple biological functions that include induction of pain, effects on many smooth muscle types, and lowering systemic blood pressure. While most BRPs are Bradykinin Receptor agonists, some have curiously been found to be exquisite antagonists, such as the maximakinin gene-related peptide, kinestatin—a specific Bradykinin B2-Receptor antagonist from the skin of the giant fire-bellied toad, Bombina maxima. Here, we describe the identification, structural and functional characterization of a heptadecapeptide (DYTIRTRLHQGLSRKIV), named ranakinestatin-PPF, from the skin of the Chinese ranid frog, Pelophylax plancyi fukienensis, representing a prototype of a novel class of Bradykinin B2-Receptor specific antagonist. Using a preconstricted preparation of rat tail arterial smooth muscle, a single dose of 10−6 M of the peptide effectively inhibited the dose-dependent relaxation effect of Bradykinin between 10−11 M and 10−5 M and subsequently, this effect was pharmacologically-characterized using specific Bradykinin B1- (desArg-HOE140) and B2-Receptor (HOE140) antagonists; the data from which demonstrated that the antagonism of the novel peptide was mediated through B2-Receptors. Ranakinestatin—PPF—thus represents a prototype of an amphibian skin peptide family that functions as a Bradykinin B2-Receptor antagonist herein demonstrated using mammalian vascular smooth muscle.
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helokinestatin a new Bradykinin B2 Receptor antagonist decapeptide from lizard venom
Peptides, 2008Co-Authors: Hang Fai Kwok, Tianbao Chen, Martin Orourke, Craig Ivanyi, David G Hirst, C. ShawAbstract:Abstract Synthetic Bradykinin antagonist peptides/peptoids have been powerful tools for delineating the roles of kinins in both normal physiology and in pathological states. Here, we report the identification of a novel, naturally occurring Bradykinin B2 Receptor antagonist peptide, helokinestatin, isolated and structurally characterized from the venoms of helodermatid lizards—the Gila monster (Heloderma suspectum) and the Mexican beaded lizard (Heloderma horridum). The primary structure of the peptide was established by a combination of microsequencing and mass spectroscopy as Gly-Pro-Pro-Tyr-Gln-Pro-Leu-Val-Pro-Arg (Mr 1122.62). A synthetic replicate of helokinestatin was found to inhibit Bradykinin-induced vasorelaxation of phenylephrine pre-constricted rat tail artery smooth muscle, mediated by the B2 Receptor sub-type, in a dose-dependent manner. Natural selection, that generates functional optimization of predatory reptile venom peptides, can potentially provide new insights for drug lead design or for normal physiological or pathophysiological processes.
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kinestatin a novel Bradykinin B2 Receptor antagonist peptide from the skin secretion of the chinese toad bombina maxima
Regulatory Peptides, 2003Co-Authors: Tianbao Chen, Martin Orourke, David G Hirst, David F Orr, Daniel J M Coulter, Pingfan Rao, C. ShawAbstract:We have isolated a novel Bradykinin B2-Receptor antagonist peptide, kinestatin, from toad (Bombina maxima) defensive skin secretion. Mass spectroscopy established a molecular mass of 931.56 Da and a provisional structure: pGlu-Leu/Ile-Pro-Gly-Leu/Ile-Gly-Pro-Leu/IleArg.amide. The unmodified sequence, -QIPGLGPLRG-, was located at the C-terminus of a 116-amino-acid residue open-reading frame following interrogation of a sequenced B. maxima skin cDNA library database. This confirmed the presence of appropriate primary structural attributes for the observed post-translational modifications present on the mature peptide and established residue 2 as Ile and residues 5/8 as Leu. Kinestatin represents a prototype novel peptide from amphibian skin. D 2003 Elsevier B.V. All rights reserved.
Jie Zhang - One of the best experts on this subject based on the ideXlab platform.
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Bradykinin B2-Receptor-mediated positive chronotropic effect of Bradykinin in isolated rat atria.
Journal of Cardiovascular Pharmacology, 1998Co-Authors: Qun Li, Juan F. Loro, Martin Pfaffendorf, Jie Zhang, Pieter A. Van ZwietenAbstract:Summary: The positive chronotropic effect of Bradykinin was investigated in isolated spontaneously beating atria of the rat. Cumulative additions of Bradykinin (0.3-100 nM) caused a concentration-dependent increase in the beating rate of the atria by maximally 35 ± 4 beats/min, ∼25% of the 1 μM isoprenaline-induced maximal responses. In contrast, the active metabolite of Bradykinin and selective Bradykinin B1-Receptor agonist, Des-Arg9-Bradykinin, did not influence the spontaneous frequency of beating. Propranolol (1 μM) combined with prazosin (1 μM) did not affect the positive chronotropic effect of Bradykinin. A selective Bradykinin B2-Receptor antagonist, Hoe 140, concentration-dependently shifted the response curves for Bradykinin to the right, whereas the Bradykinin B1-Receptor antagonist, Lys-[Leu8]Des-Arg9-Bradykinin had no effect. The tachycardic responses to Bradykinin were potentiated by ramipril, and angiotensin-converting enzyme/kininase II inhibitor, but not affected by Nω-nitro-L-arginine methyl ester hydrochloride, a nitric oxide synthesis inhibitor. Indomethacin and meclofenamate, two cyclooxygenase inhibitors, abolished the Bradykinin-induced chronotropic effect. These results indicate that exogenous Bradykinin induces a positive chronotropic effect that occurs independent of adrenoceptors. The Bradykinin-induced chronotropic effect is mediated by Bradykinin B2 Receptors, whereas B1 Receptors do not play a role in mediating this effect. Prostaglandins but not nitric oxide appear to be involved in Bradykinin-induced positive chronotropic effect.
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Bradykinin B2-Receptor-mediated positive chronotropic effect of Bradykinin in isolated rat atria
Journal of cardiovascular pharmacology, 1998Co-Authors: Jie Zhang, Juan F. Loro, Martin Pfaffendorf, Pieter A. Van ZwietenAbstract:The positive chronotropic effect of Bradykinin was investigated in isolated spontaneously beating atria of the rat. Cumulative additions of Bradykinin (0.3-100 nM) caused a concentration-dependent increase in the beating rate of the atria by maximally 35+/-4 beats/min, approximately 25% of the 1 microM isoprenaline-induced maximal responses. In contrast, the active metabolite of Bradykinin and selective Bradykinin B1-Receptor agonist, Des-Arg9-Bradykinin, did not influence the spontaneous frequency of beating. Propranolol (1 microM) combined with prazosin (1 microM) did not affect the positive chronotropic effect of Bradykinin. A selective Bradykinin B2-Receptor antagonist, Hoe 140, concentration-dependently shifted the response curves for Bradykinin to the right, whereas the Bradykinin B1-Receptor antagonist, Lys-[Leu8]Des-Arg9-Bradykinin had no effect. The tachycardic responses to Bradykinin were potentiated by ramipril, an angiotensin-converting enzyme/kininase II inhibitor, but not affected by Nomega-nitro-L-arginine methyl ester hydrochloride, a nitric oxide synthesis inhibitor. Indomethacin and meclofenamate, two cyclooxygenase inhibitors, abolished the Bradykinin-induced chronotropic effect. These results indicate that exogenous Bradykinin induces a positive chronotropic effect that occurs independent of adrenoceptors. The Bradykinin-induced chronotropic effect is mediated by Bradykinin B2 Receptors, whereas B1 Receptors do not play a role in mediating this effect. Prostaglandins but not nitric oxide appear to be involved in Bradykinin-induced positive chronotropic effect.
Jean-loup Bascands - One of the best experts on this subject based on the ideXlab platform.
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Direct protein–protein interaction between PLCγ1 and the Bradykinin B2 Receptor—Importance of growth conditions
Biochemical and biophysical research communications, 2005Co-Authors: Johan Duchene, Christiane Pecher, Jean-pierre Girolami, Jean-loup Bascands, Sharmila D. Chauhan, Frédéric Lopez, Jean-pierre Estève, Joost P. SchanstraAbstract:Abstract Recently, we have described a novel protein–protein interaction between the G-protein coupled Bradykinin B2 Receptor and tyrosine phosphatase SHP-2 via an immunoReceptor tyrosine-based inhibition motif (ITIM) sequence located in the C-terminal part of the B2 Receptor and the Src homology (SH2) domains of SHP-2. Here we show that phospholipase C (PLC)γ1, another SH2 domain containing protein, can also interact with this ITIM sequence. Using surface plasmon resonance analysis, we observed that PLCγ1 interacted with a peptide containing the phosphorylated form of the Bradykinin B2 Receptor ITIM sequence. In CHO cells expressing the wild-type B2 Receptor, Bradykinin-induced transient recruitment and activation of PLCγ1. Interestingly, this interaction was only observed in quiescent and not in proliferating cells. Mutation of the key ITIM residue abolished this interaction with and activation of PLCγ1. Finally we also identified Bradykinin-induced PLCγ1 recruitment and activation in primary culture renal mesangial cells.
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Decreased renal NO excretion and reduced glomerular tuft area in mice lacking the Bradykinin B2 Receptor.
American journal of physiology. Heart and circulatory physiology, 2003Co-Authors: Joost P. Schanstra, Jean-pierre Girolami, Johan Duchene, Françoise Praddaude, Patrick Bruneval, Ivan Tack, Jacques Chevalier, Jean-loup BascandsAbstract:Bradykinin B2 Receptor knockout mice (B2 −/−) have been useful to study the role of Bradykinin under pathological conditions. With the use of these mice, it was shown that Bradykinin plays an impor...
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In vivo Bradykinin B2 Receptor activation reduces renal fibrosis
The Journal of clinical investigation, 2002Co-Authors: Joost P. Schanstra, Eric Neau, Pascale Drogoz, Miguel Angel Arévalo Gómez, José Miguel Lopez Novoa, Denis Calise, Christiane Pecher, Michael Bader, Jean-pierre Girolami, Jean-loup BascandsAbstract:Angiotensin-converting enzyme (ACE) inhibitors reduce the progression of various fibrotic renal diseases both in humans and in animal models. Unilateral ureteral obstruction (UUO) is an animal model of accelerated renal tubulointerstitial fibrosis that is attenuated by ACE inhibition. Although ACE inhibitors increase Bradykinin concentrations in addition to their effect on angiotensin II formation, the role of Bradykinin in renal fibrosis has not been studied. We show here that genetic ablation (B2(-/-) mice) or pharmacological blockade of the Bradykinin B2 Receptor increases UUO-induced interstitial fibrosis in mice, whereas transgenic rats expressing increased endogenous Bradykinin show reduced UUO-induced interstitial fibrosis. The increased interstitial fibrosis in B2(-/-) mice was accompanied by a decreased activity of plasminogen activators (PAs) and metalloproteinase-2 (MMP-2), enzymes involved in ECM degradation, suggesting that the protective effects of Bradykinin involve activation of a B2 Receptor/PA/MMP-2 cascade. This ability of Bradykinin to increase PA activity was confirmed in primary culture proximal tubular cells. Thus, in both mice and rats, Bradykinin B2 Receptor activation reduces renal tubulointerstitial fibrosis in vivo, most likely by increasing ECM degradation.
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30 years happy birthday gpcr the Bradykinin B2 Receptor an alternative and antiproliferative pathway
Nephrologie, 2002Co-Authors: Johan Duchene, Jean-loup Bascands, J P Schanstra, Eric Cellier, Jean-pierre GirolamiAbstract:The Bradykinin B2 Receptor which belongs to the G-protein-coupled Receptor (GPCR) family is known for its proliferative effects. The mitogenic signalling pathways used are "classical" pathways for GPCRs. Recent data from our laboratory show that Bradykinin can also induce anti-mitogenic effects in proliferating cells using an "alternative" signal transduction pathway involving a protein tyrosine phosphatase. Besides this alternative signalling pathway for the B2 Receptor, a novel concept of GPCR signalling is described.
J.-p. Gies - One of the best experts on this subject based on the ideXlab platform.
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PLA2 phosphorylation and cyclooxygenase-2 induction, through p38 MAP kinase pathway, is involved in the IL-1beta-induced Bradykinin B2 Receptor gene transcription.
Naunyn-Schmiedeberg's archives of pharmacology, 2000Co-Authors: Fabien Schmidlin, Yves Landry, S. Loeffler, C. Bertrand, J.-p. GiesAbstract:We hypothesized that inflammatory mediators such as interleukin-1β (IL-1β) might be responsible for the hyperreactivity to Bradykinin observed in asthmatic patients. We reported previously that Il-1β induced a prostanoid-dependent increase in the density of Bradykinin B2 Receptors in cultured human bronchial smooth muscle cells. Our experiments demonstrate that the rapid prostaglandin E2 (PGE2) synthesis induced by IL-1β is abolished by cycloheximide, suggesting the involvement of protein synthesis. The formation of PGE2 is preceded by the phosphorylation of cPLA2 and the expression of cyclooxygenase-2 (Cox-2). The inhibition of p38 MAP kinase inhibited PGE2 synthesis, cPLA2 phosphorylation and abolished Cox-2 expression. The inhibition of Cox-2 expression correlated with a decrease of Bradykinin B2 Receptor expression. These data demonstrate that the activation of p38 MAP kinase elicited by IL-1β leads to the phosphorylation of cPLA2 and Cox-2 overexpression, allowing rapid synthesis of PGE2 as a prerequisite for Bradykinin B2 gene expression in human bronchial smooth muscle cells which could explain the hyperresponsiveness of asthmatic patients to Bradykinin.
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Glucocorticoids increase Bradykinin B2 Receptor gene transcription in cultured guinea-pig tracheal smooth muscle cells.
Naunyn-Schmiedeberg's archives of pharmacology, 1999Co-Authors: Didier Scherrer, Fabien Schmidlin, El-bdaoui Haddad, Olivier Kassel, Yves Landry, J.-p. GiesAbstract:We investigated the effect of the glucocorticoid methylprednisolone on the modulation of the expression of the Bradykinin B2 Receptors in cultured, guinea-pig, tracheal, smooth muscle cells. These Receptors are implicated in the pathogenesis of human asthma. Untreated cells expressed a single population of binding sites for [3H]Bradykinin with a dissociation constant, K d, of 87.7±12.0 pM and a maximum binding site density, B max, of 245.4±71 fmol/mg protein. Treatment of the cultured guinea-pig tracheal smooth muscle cells with methylprednisolone 10–5 M for 6 h increased the number of Bradykinin Receptors; this response reached a maximum of 78% and returned to the basal value after 12 h. Bradykinin (10–12 M) elicited a sixfold higher calcium level in treated cells than in control cells. To investigate Bradykinin B2 Receptor mRNA expression in guinea-pig cells, we used the reverse transcription polymerase chain reaction (RT-PCR) technique to synthesize a specific Bradykinin B2 cDNA probe of 296 bp corresponding to nucleotides 456–751 of the human sequence. This guinea-pig cDNA had 88%, 86% and 83% homology with the corresponding human, mouse and rat sequences, respectively, but no homology with any other known sequences. Following methylprednisolone treatment, Northern blot hybridization indicated that mRNA increased fourfold after 3 h compared with control cells, and returned to basal level within 7 h. The rate of gene transcription, assessed by nuclear run-on assays, increased fourfold after 3 h treatment with 10–5 M methylprednisolone. These results indicate that glucocorticoids induce early up-regulation of Bradykinin B2 Receptors in cultured guinea-pig tracheal smooth muscle cells by increasing the rate of transcription of the Bradykinin B2 Receptor gene.