Dissertations / Theses: 'Bradykinin'

1

UENO, Tomoyuki, Yasuko KOZAKI, and Kazue MIZUMURA. "Increased Expression of mRNA for B1 and B2 Bradykinin Receptors in the Skin of Adjuvant Inoculated Rats." Research Institute of Environmental Medicine, Nagoya University, 2002. http://hdl.handle.net/2237/2787.

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2

Willer, Elizabeth Jane. "Control of B2 bradykinin receptor gene expression." Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286487.

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3

Owen, Penelope Jane. "Bradykinin stimulation of bovine adrenal chromaffin cells." Thesis, University of Leicester, 1991. http://hdl.handle.net/2381/33600.

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Cultured bovine adrenal chromaffin cells provide a useful model of stimulus secretion coupling and respond to cholinergic agonists by secreting catecholamines. Work in this thesis concentrates on the responses to a non-cholinergic agonist, bradykinin. Bradykinin as shown to stimulate a two phase, dose dependent increase in catecholamine release which is mediated by a receptor of the B2 subtype. Calcium entry is shown to be required for release to occur but studies with various calcium channel blockers suggest that, in contrast to the response to potassium, a non-voltage sensitive calcium channel is involved. Other possible alternatives are discussed. As bradykinin stimulated an increase in inositol phosphate production, I attempted to measure the production of the other product of phospholipase C action on inositol phospholipids, diacylglycerol, in order to evaluate its possible role in the release response. This was attempted using both mass measurement, by the diacylglycerol kinase assay, and lipid labelling techniques. No increases in diacylglycerol in response to bradykinin were observed, even in the presence of inhibitors of diacylglycerol breakdown, which were able to increase basal diacylglycerol levels when added alone. These inhibitors, along with TPA, were used to evaluate the possible mechanism of action of protein kinase C in chromaffin cells, eg. feedback regulation or stimulation of release mechanisms. Failure to detect rises in diacylglycerol in response to bradykinin led to the final section of this work which looks at the production of one of the metabolic products of diacylglycerol breakdown, phosphatidic acid. Bradykinin is shown to stimulate a rapid, dose dependent increase in phosphatidic acid in chromaffin cells, which is, partially independent of extracellular calcium, independent of protein kinase C activation, and may be G-protein mediated. Studies of the route of formation of the phosphatidic acid show that phospholipase D is not involved and that inositol phospholipids or phosphatidylcholine are unlikely to be the main substrates for a phospholipase C mediated route, leaving the possibility of phospholipase C action on an alternative phospholipid. Finally the possible role of this production of phosphatidic acid in the chromaffin cell is discussed.

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4

Holz, Alexander. "Theoretische Untersuchungen zum Bindungsmodus nichtpeptidischer Bradykinin B2 Rezeptorantagonisten." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=968529038.

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5

Waldner, Maximilian. "Die Wirkung von Bradykinin auf die zerebrale Mikrozirkulation." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-71745.

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6

Witherow, Fraser N. "Bradykinin : vasomotor tone and endogenous fibrinolysis in man." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/29426.

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Bradykinin is a nonapetide released into plasma during the contact phase of blood coagulation. It has a wide variety of physiological effects including vasodilatation, tissue-type plasminogen activator (t-PA) release, inflammatory mediator, ischaemic preconditioning and vasculogenesis. It is inactivated in plasma by angiotensinconverting enzyme (ACE). Inhibition of this enzyme has been shown to be beneficial in a variety of cardiovascular disorders including heart failure and hypertension, and it is clear that this benefit is not due entirely to reduction in the bioavailability of angiotensin II. We hypothesised that • bradykinin is a vasodilator and stimulates endothelial t-PA release via a specific receptor and that this effect is augmented by ACE inhibition. • in patients with heart failure, bradykinin contributes to peripheral and systemic vascular tone during treatment with ACE inhibition. Forearm blood flow was measured using bilateral forearm plethysmography during intrabrachial drug infusion. Bilateral venous cannulae were inserted to perform blood sampling for estimation of plasma t-PA and plasminogen activator inhibitor 1 (PAI- 1) concentrations. Cardiac output was measured with pulmonary artery catheterisation. The novel peptide bradykinin receptor antagonist, B9340, was used to oppose the effects of bradykinin. Studies were performed in healthy volunteers • to demonstrate the pharmacodynamics of B9340 and to demonstrate the selectivity of B9340 in opposing bradykinin-induced t-PA release. • to demonstrate the safety and tolerability of systemic intravenous B9340 administration. Studies were performed in patients with heart failure • to demonstrate the effect of ACE inhibition on endothelial t-PA release. • to demonstrate the effect of bradykinin antagonism on peripheral and systemic vascular tone in patients treated with ACE inhibition and angiotensin receptor blockade. Results In healthy volunteers • Bradykinin and substance P caused dose-dependent vasodilatation in the infused forearm (p < 0.001). B9340 caused a dose-dependent inhibition of bradykinin-induced forearm vasodilatation and t-PA release (p < 0.001) without affecting substance P-induced vasodilatation or t-PA release (p=NS). B9340 caused a reversible inhibition of bradykinin-induced vasodilatation (p < 0.001) with a rapid onset and offset of action. Intravenous systemic B9340 administration inhibited the local bradykinin-induced forearm vasodilatation in a dose-dependent manner. In patients with heart failure • bradykinin and substance P caused dose-dependent vasodilatation and release of t-PA from the infused forearm (p < 0.05). Long-term ACE inhibitor therapy caused an increase in forearm vasodilatation (p < 0.05) and t-PA release (p < 0.001) during bradykinin, but not substance P, infusion. • incremental doses of B9340 caused a dose-dependent reduction in forearm blood flow (p < 0.01). After withdrawal of ACE inhibitor therapy, B9340 produced no significant change in forearm blood flow. • systemic intravenous B9340 administration resulted in greater mean arterial pressure, systemic vascular resistance, pulmonary arterial wedge pressure, and mean pulmonary arterial pressure during ACE inhibitor therapy compared with losartan therapy (p < 0.005, p < 0.07, p < 0.0001, and p < 0.05 respectively) or placebo infusion (p < 0.005 for all). We have shown that bradykinin is a potent vasodilator that stimulates endogenous t-PA release and that these effects are receptor specific and can be blocked by a bradykinin receptor antagonist. We have also shown that bradykinin does not contribute to peripheral or systemic vascular tone in health but does contribute to peripheral and systemic vascular tone in patients with heart failure treated with chronic ACE inhibition. We believe this suggests that many of the beneficial actions of ACE inhibition are mediated through bradykinin.

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7

Blair, Alan. "Role of bradykinin in virus-induced airway inflammation." Thesis, Cardiff University, 2009. http://orca.cf.ac.uk/54363/.

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Asthma is a chronic inflammatory disease of the airways and viral infections account for the majority of exacerbations and may play a role in its pathogenesis. Bradykinin levels are increased in the lungs of asthmatics and inhaled bradykinin produces bronchoconstriction in asthmatic but not in normal patients. In this study, guinea-pigs were inoculated with parainfluenza and influenza virus to establish airways inflammation and hyperreactivity. The role of bradykinin in the parainfluenza model was examined by using the tissue kallikrein inhibitor, FE999024, and the bradykinin B2 receptor antagonist, MEN16132. Firstly, the effects of bradykinin inhalation in conscious guinea-pigs were characterized by using inhibitors of its breakdown and selective antagonists. Inhaled bradykinin produced a bronchoconstriction only after treatment with the inhibitors of angiotensin converting enzyme and/or neutral endopeptidase, captopril and phosphoramidon respectively. Inhaled bradykinin also increased inflammatory cell influx to the lungs when its breakdown was inhibited with both drugs. Cell influx and bronchoconstriction were blocked by the B2 receptor antagonists icatibant and MEN16132. These responses were therefore B2 receptor-mediated. In ovalbumin sensitized guinea-pigs, inhaled ovalbumin produced early and late asthmatic responses, inflammatory cell influx and airway hyperreactivity to histamine. These were inhibited by dexamethasone. Bradykinin caused bronchoconstriction without using metabolism inhibitors, indicating airways hyperreactivity to bradykinin. Parainfluenza-3 and influenza caused inflammatory cell influx and airways hyperreactivity to histamine. These were inhibited by FE999024, MEN16132 and dexamethasone. Parainfluenza-3 virus inoculated into sensitized guinea-pigs exacerbated the response to inhaled ovalbumin, with a prolonged bronchconstriction replacing early and late phases. This was resistant to dexamethasone. This study supports a role for bradykinin in virus-induced lung inflammation and the use of inhibitors of bradykinin for potential treatment of airway inflammation.

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8

Yang, M. "Catabolism and bioactivity of bradykinin and related peptides." Thesis, Queen's University Belfast, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.557857.

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Bradykinin and related peptides (BRPs) are common components of amphibian defensive skin secretions, particularly in ranid and phyllomedusine frogs and in bombinid toads. BRPs are known to be highly vasoactive with some possessing potent effects on blood vessel formation (angiogenesis) - a process known to be initiated by direct effects on endothelial cells. Human microvessel endothelial (HMEC) cells are a stable laboratory cell line often used for preliminary screening in such studies of BRP function. Since these cells are the starting points for fundamental biological studies, we examined their catabolism of bradykinin (BK) and maximakinin (MK). MK represents an N-terminally extended version of the former but with higher potency. Both BK and MK were broken down by proteases present on HMEC cells with half-lives of 5h and 2h, respectively. However, as two major metabolites of MK retained the receptor-active site of BK, the true half-life of non- active metabolite generation was 5h (BK) and 9h (MK). Bradykinin antagonists, kinestatin and QUB919, both from amphibian skin, were not degraded by HMEC cells and their presence did not interfere with the degradation of BK or MK. Using primer sets designed for bradykinin Bland B2 receptors, transcripts of appropriate size were amplified from an HMEC cell cDNA library. Bradykinin-related peptides are thus catabolised in different ways by HMEC cells and the cells were shown to contain polyadenylated mRNAs for both bradykinin receptor sub-types, Bland B2. To examine other functions of BRPs, we screened reverse phase HPLC fractions of venoms and defensive skin secretions to identify, structurally characterise and ultimately chemically-synthesise novel peptides to examine their effects on bradykinin activity using smooth muscle bioassays. Many BRPs exhibited anti- cancer and anti-microbial functions in our experiments giving us a broader perspective for further research in the BRP field. · ';.

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Polosa, Riccardo. "The mechanism of bradykinin-induced bronchoconstriction in asthma." Thesis, University of Southampton, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295948.

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10

Ljunggren, Östen. "Involvement of bradykinin in inflammation induced bone resorption." Umeå : University of Umeå, 1991. http://catalog.hathitrust.org/api/volumes/oclc/24493228.html.

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11

Hall, Sara M. "Bradykinin Ligands and Receptors Involved in Neuropathic Pain." Diss., The University of Arizona, 2015. http://hdl.handle.net/10150/578606.

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Neuropathic pain is a prevalent disease with no effective, safe treatments and limited knowledge on the mechanisms involved. One target for neuropathic pain treatment may be the blockade of Dynorphin A (Dyn A). Dyn A is a unique endogenous ligand that possesses well-known neuroinhibitory effects via opioid receptors and neuroexcitatory effects that are mediated through the bradykinin 2 receptors (B2Rs). Extensive SAR was carried out to develop a ligand for the blockade of the excitatory actions of Dyn A at the B2R. A lead ligand was able to block Dyn A-induced hyperalgesia in naïve animals and was effective in a neuropathic pain model. However, the ligand was susceptible to enzymatic degradation. In an effort to increase the stability, modifications of the ligand using non-natural amino acids were performed. Analogues substituted at or near the N-terminus with a D-isomer retained binding at the receptor as well as provided a large increase in stability. These ligands were also found to be non-toxic in a cell toxicity assay. Dyn A has been found to not activate the classical signaling of the B2R, PI hydrolysis or Ca²⁺ mobilization. In an effort to determine Dyn A's signaling, a study was done examining up-regulation of phosphorylated proteins. It was found that Dyn A did not activate; pERK, 7 PKC isoforms or PKA. A well known B2R antagonist, HOE140, was found to have low affinity at rat and guinea pig brain B2Rs but high affinity in the guinea pig ileum. Further examination revealed that this discrepancy in binding may arise from a different isoform of the B2R that has not been previously examined. To date, we have discovered Dyn A analogues that have high affinity for the B2R, are very stable, and have low toxicity. The signaling pathway is still not fully understood, but further studies are underway. Also, there is evidence that the B2R in which the analogues are interacting at may be a different form than what has previously been described. Targeting this different isoform of the B2R with our current stable ligands may provide beneficial therapeutics for the treatment of neuropathic pain without the cardiovascular liabilities.

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12

Bromée, Torun. "Evolution and pharmacology of receptors for bradykinin and neuropeptide Y in vertebrates /." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6085.

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13

Dear, James William. "Characterisation of the kinin receptor in the human nasal airway and its role in allergic rhinitis." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244065.

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14

Yim, Cynthia. "Effects of ovokinin on isolated aortas of guinea pigs, normotensive and spontaneously hypertensive rats." Thesis, Virginia Tech, 1998. http://hdl.handle.net/10919/36796.

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Ovokinin, a peptide recently isolated from an enzymatic digest of ovalbumin, has been shown to mediate vasorelaxation of the canine mesenteric artery through bradykinin B1 receptors. Bradykinin can mediate both vasorelaxation and vasocontraction depending upon the tissue or species investigated. The aim of this study was to characterize ovokinin further by determining whether the effects of this peptide, like bradykinin, vary when using different species and tissue preparations as well as different contracting agents. Isolated aortic rings from guinea pigs, normotensive rats, and spontaneously hypertensive rats were exposed to phenylephrine, prostaglandin F2a, potassium chloride, or bradykinin. Bradykinin contracted guinea pig and spontaneously hypertensive rat aortas, however, it had no effect on normotensive rat aortas. In this study, ovokinin did not exhibit activity in any of the preparations except in guinea pigs, where it potentiated the contraction elicited by bradykinin only. This potentiation was blocked when rings were pretreated with captopril, a kininase II inhibitor. Ovokinin may also exhibit slight vasorelaxing activity in spontaneously hypertensive rat aortas precontracted with prostaglandin F2a. These findings suggest that, like bradykinin, the effects of ovokinin are species- and tissue-dependent. The action of ovokinin on the guinea pig aorta may involve kininase II, which is partly responsible for the degradation of bradykinin and other kinins.

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15

Brennan, Hugh. "Bradykinin induced contraction of human gallbladder muscle in vitro." Thesis, University of Southampton, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.403747.

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16

Voegeli, David. "The inhibition of bradykinin-induced dermal inflammation by cetirizine." Thesis, University of Southampton, 2001. https://eprints.soton.ac.uk/57950/.

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This work was designed to explore the effect of cetirizine on mediator release secondary to intradermal bradykinin challenge in normal human skin. On intradermal injection, bradykinin produces a dose-dependant weal and flare response similar visually to that produced by histamine, suggesting that histamine release is involved in mediating the cutaneous response. This is further supported by the fact that premedication with cetirizine significantly inhibits both the bradykinin and histamine weal and flare. However microdialysis demonstrated that there is insignificant histamine release following bradykinin, and SLDI showed that the weal and flares produced by both histamine and bradykinin are different in nature, suggesting that other mediators, such as prostanoids or NO are involved. Although both prostanoid synthesis and NO release were observed following bradykinin, cetirizine failed to have any effect on the levels measured, suggesting that these are not the major mediators responsible for the bradykinin response. Cetirizine was shown to be able to inhibit the cutaneous responses induced by a number of agonists, namely bradykinin, histamine, and methacholine. All of these act via a specific GPCR, and each one having an alpha subunit of the Gq/11 variety. Therefore it is postulated that the bradykinin-induced weal and flare is mediated by activation of B2-kinin receptors located on sensory neurones, resulting in the release of neuropeptides, and that inhibition of this response is achieved by a direct inhibition of Gq/11 G-proteins, their regulatory proteins or modulation of a common second messenger system.

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17

Benner, Susanne. "Freisetzung von Bradykinin aus High Molecular Weight Kininogen durch Plasmakallikrein /." [S.l.] : [s.n.], 1994. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=10910.

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18

Malmberg, Michelle. "Funktionella och farmakologiskakonsekvenser av Bradykinin B1-och B2-receptor samuttryck." Thesis, Umeå universitet, Kemiska institutionen, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-101863.

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Ebrahim, Zaileen. "Cardioprotective actions of bradykinin in the normal and hypertrophied myocardium." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249678.

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20

Plevin, Robin John. "Studies on angiotensin II and bradykinin receptors in epithelial tissues." Thesis, University of Southampton, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278664.

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21

Alfituri, A. M. "Effects of bradykinin on calcium signalling and contractility of ureter." Thesis, University of Liverpool, 2017. http://livrepository.liverpool.ac.uk/3011383/.

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The understanding of the mechanism, by which bradykinin (BK) effects ureteric contractility, is limited. The primary aim of this study was to determine the expression and the distribution of B2 receptors along the length of the ureter and study the effects of BK on Ca2+ signalling and contractile activity of the rat ureteric smooth muscle. Both the Ca2+-dependent and Ca2+-independent pathways, underlying the stimulant action of BK on the ureteric smooth muscle, have been investigated. Immunohistochemistry was used to identify the presence and the distribution of B2 receptors along the ureter. Confocal imaging combined with force measurements under different physiological conditions was used to study the effects of BK on Ca2+ signalling and force of the ureteric smooth muscle in situ. The effect of the selective blocker of Rho-associated kinase, Y-27632, on force/ Ca2+ relationship was investigated. It was found that the distribution of the B2 receptors is non-homologous along the length of the rat ureter, with the expression being greater in the upper ureter and lowest in the middle and the lower ureter. It was found that BK caused a complex contractile response, consisting of an initial phasic component, associated with the Ca2+ release from the store, which appeared as asynchronous Ca2+ waves, followed by a sustained component, associated with Ca2+ entry via store/receptor operated Ca2+ channels that was superimposed by multiple phasic contractions, associated with propagating intercellular Ca2+ waves. The L-type Ca2+ channel blocker, Nifedipine, selectively blocked the intercellular Ca2+ wave and the repeated phasic contraction, but had no effect on the initial phasic contraction, associated with the Ca2+ release from the sarcoplasmic reticulum. Nifedipine, also had no effect on the sustained slow component, associated with the Ca2+ entry via store/receptor operated Ca2+ channels. Y-27632 had no effects on the Ca2+ signalling, associated with the Ca2+ release from the store or the Ca2+ entry via store/receptor operated Ca2+ channels, but had significant inhibitory effects on the initial phasic and sustained tonic component of BK-induced contractile response. There was a significant reduction in the amplitude and an increase in the rate of relaxation of the initial phasic component, suggesting an increase of the activity of myosin light chain phosphatase, responsible for dephosphorylation of MLC20 and relaxation of force in the smooth muscles. Collectively, the data obtained indicate that both Ca2+-dependent and Ca2+-independent mechanisms are involved in BK-induced stimulant action on the rat ureteric smooth muscle.

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22

Jones, Caroline Jane. "Cloning and regulation of the rat bradykinin B1 receptor gene." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.392133.

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23

Chen, Qingmin. "Bradykinin Receptors Mediate Dynorphin Pronociceptive Action To Produce Persistent Pain." Diss., The University of Arizona, 2007. http://hdl.handle.net/10150/195460.

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Intrathecal injection of dynorphin or des-Tyr-dynorphin fragments, which do not bind to opioid receptors, produce tactile and thermal hypersensitivity in rodents. The maintenance, but not initiation, of experimental neuropathic pain depends upon pronociceptive effects of elevated levels of spinal dynorphin. Recent findings implicated a direct excitatory action of dynorphin A at bradykinin receptors in vitro. Here, the possibility that the pronociceptive actions of pharmacological dynorphin or of pathological levels of endogenous spinal dynorphin are mediated by interaction with bradykinin receptors was explored.While spinal administration of a wide range of bradykinin did not produce hyperalgesia in rats, intrathecal injection of non-opioid des-tyrosyl-dynorphin A(2-13) produced reversible tactile and thermal hypersensitivities that were reversed by bradykinin receptor antagonists. Dynorphin-induced behavioral hyperesthesias were observed in bradykinin B2 receptor wild-type but not in B2 receptor knockout mice. Spinal administration or infusion of B1, and especially B2, receptor antagonists reversed experimental neuropathic pain behaviors in rats with peripheral nerve injury but only when the antagonists were given at times at which dynorphin was upregulated. After nerve injury, both B1 and B2 receptor mRNA were increased in the dorsal root ganglion, but not in the spinal cord. While a marked increase in mRNA expression for prodynorphin in the lumbar spinal cord was found following nerve injury, expression of mRNA for kininogen was below detection levels. The possible interaction of spinal dynorphin with bradykinin receptors as a basis of the pronociceptive action of this peptide was further tested in the CFA-induced inflammatory pain and DBTC-induced pancreatitis pain. Intrathecal administration of bradykinin receptor antagonists or dynorphin antiserum reversed DBTC-induced abdominal hypersensitivity and CFA-induced hyperalgesia only when spinal dynorphin or prodynorphin is upregulated. The antihyperalgesic effect of the bradykinin receptor antagonists was not due to de novo production of bradykinin.Taken together, our results unravel a novel, non-opioid molecular target of dynorphin, and indicate that dynorphin acts at bradykinin receptors to produce persistent psin in the pathological pain states. This novel pronociceptive mechanism offers new approaches to the development of therapy for pathological pain states.

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Rajakulasingam, Karalasingam. "The effects, mechanism and actions of kinins in rhinitis and asthma." Thesis, University of Southampton, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243150.

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Williams, Ruth J. "Is the neutrophil an inflammation signalling cell in rheumatoid arthritis?" Thesis, University of Bristol, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337695.

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Khosravani, Farbod [Verfasser], and Georg [Akademischer Betreuer] Kojda. "Regulation der endothelialen Permeabilität durch Bradykinin / Farbod Khosravani ; Betreuer: Georg Kojda." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2018. http://d-nb.info/1172968039/34.

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Said, Najeeb Barrah. "The design and synthesis of non-peptide bradykinin B2 receptor antagonists." Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285827.

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Mak, Stephanie Wai Yin. "Modulation of temperature sensitive ion channels TRPV1 and TRPM8 by Bradykinin." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611520.

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Bouhadfane, Mouloud. "Propriétés électriques bistables des motoneurones de la moelle épinière : Identification des mécanismes ioniques sous-jacents." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM5030/document.

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La posture, composante statique du contrôle moteur permettant une position érigée du corps, repose sur une décharge tonique des motoneurones innervant nos muscles antigravitaires. La décharge prend la forme de « potentiel de plateau » au niveau de motoneurones matures chez de nombreux vertébrés. Pour déterminer une éventuelle concordance entre l'émergence des propriétés de plateau et le développement postural, notre travail a eu pour but d'étudier la maturation et la nature ionique des potentiels de plateau des motoneurones innervant le muscle triceps surae (extenseur de la cheville) chez le rat nouveau-né.La réalisation de ces travaux de thèse nous a permis de dégager un mécanisme fondamental dans la genèse des propriétés de plateau des motoneurones lombaires. Ce mécanisme dont le fondement repose sur l'activation d'un « ménage à trois » jouerait un rôle majeur dans le développement moteur chez le rat. Dans la mesure où les potentiels de plateau des motoneurones sont fortement perturbés à la suite d'une lésion médullaire, cette avancée scientifique permettra éventuellement de mieux comprendre l'origine de certains déficits sensori-moteurs (spasticité, hyperalgésie...) et le développement de nouvelles stratégies thérapeutiques
Posture allowing an erect posture of the body relies on spiking activity of motoneurons innervating antigravitary muscle. Discharge could take the form of plateau potential on mature motoneurons of numerous vertebrates. To determine a possible concordance between the emergence of plateau potential and postural control development, we studied the maturation and ionic nature of plateau potential of motoneurons innervating triceps surae muscle of neonatal rat.The conclusion of our work allows us to propose a fundamental mechanism in the genesis of plateau potential on lumbar motoneurons. This mechanism based on a "ménage a trois" seems to play an important role in the neonatal motor development. This scientific advance could eventually lead to a better understanding of the origin of some sensori-motor impairments (spasticity, hyperalgesia...) and development of therapeutic strategies

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30

Bromée, Torun. "Evolution and Pharmacology of Receptors for Bradykinin and Neuropeptide Y in Vertebrates." Doctoral thesis, Uppsala University, Department of Neuroscience, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6085.

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The bradykinin and neuropeptide Y (NPY) receptors belong to the superfamily of G-protein coupled receptors (GPCRs). The GPCRs form the largest class of therapeutic targets and it is therefore of great interest to investigate the pharmacological properties, functions and evolution of these receptors.

Bradykinin (BK) is a nonapeptide that contributes to inflammatory responses, mediates pain signals and influences blood pressure. The two bradykinin receptor subtypes B1 and B2 are well characterized in mammals, but have received little attention in non-mammals. This thesis describes the cloning and characterization of the first piscine bradykinin receptor, from the Danio rerio (zebrafish). Ligand-receptor interactions were measured as production of intracellular inositol phosphate. Zebrafish BK activated the receptor with highest potency (pEC₅₀=6.97±0.1) while mammalian BK was almost inactive. A complete alanine and D-amino acid scan of the BK peptide revealed important roles for receptor interaction for residues Gly4, Ser6, Pro7, Leu8 and Arg9. The receptor gene was mapped to chromosome 17 in the zebrafish genome in a region that shows conserved synteny to the human B1-B2 gene region on chromosome 14. The release of the zebrafish and pufferfish genomes enabled us to identify both B1 and B2 genes in Danio rerio and pufferfishes (Takifugu rubripes and Tetraodon nigroviridis) as well as the B1 gene in chicken. All of these species display conserved synteny of the gene region. Interestingly, the evolutionary rate is clearly greater for B1 than for B2. Kininogen, the precursor for bradykinin, is also located in a chromosome region with extensive conserved synteny.

Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) comprise a family of related peptides and are involved in a variety of neuronal and endocrine functions. Receptor subtypes Y6 and Y7 were cloned and pharmacologically characterized in chicken. The genes are located one megabase apart on chromosome 13 in a region with conserved synteny to human chromosome 5. Porcine PYY bound to chicken Y6 with a K_d of 0.80±0.36 nM and chicken Y7 with a K_d of 0.14±0.01 nM. The Y6 mRNA is expressed in hypothalamus, gastrointestinal tract and adipose tissue and may be involved in appetite regulation like other NPY receptors. Chicken Y7 mRNA was only detected in adrenal gland. These results may help explain why these receptors have lost function in humans.

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Feierler, Jens. "Die Funktion der Helix 8 für die Regulation des Bradykinin B2 Rezeptors." Diss., lmu, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-143470.

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Kennedy, Christopher R. J. "Signalling pathways of bradykinin-mediated arachidonic acid release in MDCK-D1 cells." Thesis, University of Ottawa (Canada), 1997. http://hdl.handle.net/10393/4074.

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An investigation was undertaken to elucidate the signal transduction pathways involved in bradykinin (BK)-mediated release of arachidonic acid (AA) from the D1 clone of Madin-Darby canine kidney cells (MDCK-D1) which display distal tubule- and cortical collecting duct principal cell-like characteristics. Prostaglandins (PG), generated subsequent to BK stimulation, are known to modulate arginine-vasopressin (AVP)-stimulated water flow across this portion of the nephron. The enzyme immediately responsible for AA release was determined to be the 85 kDa cytosolic phospholipase A$\sb2$ (cPLA$\sb2),$ since Western blots revealed the presence of this enzyme and its specific inhibition by an arachidonate analogue completely blunted BK-stimulated AA release. Additionally, in vitro PLA$\sb2$ activity could be significantly reduced by preincubating cell lysates with an antibody to this enzyme. Lastly, this in vitro activity met all the requirements specific to cPLA$\sb2,$ including activity at micromolar Ca$\sp{2+}$ concentrations and dithiotreitol (DTT)-insensitivity. The findings herein suggest the signalling route taken for BK-induced AA release involves phosphatidyicholine-specific phospholipase C (PC-PLC) as well as phospholipase D (PLD). Accordingly, production of sn-1,2-diacylglycerol (DAG) and to a lesser extent, phosphatidic acid (PA), both contribute to this release of AA by enhancing PLA$\sb2$ activity within the cellular membranes, whereas the activation of phosphatidylinositol-specific phopholipase C (PI-PLC) and subsequent inositol trisphosphate (InsP$\sb3$) production does not. While reports indicate the activation of protein kinase C (PKC) is required for epinephrine-mediated AA release in this cell line, inhibition of PKC failed to abrogate BK-stimulated AA release. On the other hand, down regulation of PKC levels via long-term incubation with phorbol ester (PMA) reduced both BK- and calcium ionophore (A23187)-induced AA release. However, both in vitro cPLA$\sb2$ activity and its phosphorylation, but not its expression, were significantly reduced subsequent to long-term PMA treatment, thereby demonstrating that this strategy falsely implicates immediate activation of PKC as being required for BK-mediated AA release. Extracellular calcium (Ca$\sp{2+})$ was also needed for AA release as blockade of receptor-operated Ca$\sp{2+}$ channels significantly decreased BK-induced AA release. In addition, a negative regulatory pathway in MDCK cells was demonstrated which diminishes BK-mediated AA release. Agents which cause elevations in adenosine-3$\sp\prime,5\sp\prime$-cyclic monophosphate (cAMP) levels, such as AVP or forskolin (FSK) and 3-isobutyl-1-methylxanthine (IBMX), were found capable of significantly reducing BK-induced AA release and in vitro PLA$\sb2$ activity. This method of inhibition could represent a physiological mechanism of negative feedback promoted by agents which increase cAMP levels within the cells of the distal tubule and collecting duct. Possible targets for inhibition are suggested in light of results obtained in the present thesis and reported by others.

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33

Kennedy, Chris R. J. "Signalling pathways of bradykinin-mediated arachidonic acid release in MDCK-D1 cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq21003.pdf.

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Patel, Avni. "Physiological effects of bradykinin in conscious lambs, is there a maturational difference?" Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ31366.pdf.

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Würner, Lisa Katharina [Verfasser]. "Effects of the inflammatory mediator bradykinin on intestinal functions / Lisa Katharina Würner." Gießen : Universitätsbibliothek, 2013. http://d-nb.info/1065463065/34.

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36

Chipperfield, Sarah. "Modulation of aquaporin 2 expression and distribution by angiotensin, bradykinin and prostaglandins." Thesis, University of Leeds, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439570.

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Yaqoob, Mohammed. "Purification and characterisation of the Bâ†2 bradykinin receptor from rat uterus." Thesis, Open University, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318672.

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Asghar, Aziz-Ur-Rehman. "Pharmacological studies of bradykinin and other inflammatory mediators in rat neural preparations." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/20542.

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This thesis tests the hypothesis that certain mediators (purines, catecholamines and bradykinin), which are known to be involved in inflammation, contribute to the sensitisation of peripheral nociceptors that occurs in chronic inflammation and hyperalgesia associated with arthritis. The major part of the studies determined the role of these substances and their pharmacological receptors in modulating discharge recorded from high threshold C-fibre mechanonociceptors (on-going or 'spontaneous', and mechanically-evoked) in normal ankle joints and in those with a monoarthritis induced by Freunds complete adjuvant (FCA). Some of the in-vitro neuropharmacological investigations were complemented by behavioural studies on intact normal and arthritic rats. Related in vitro experiments were performed involving a) extracellular 'grease gap' recordings from various peripheral nerves and b) contractile responses of the electrically-stimulated rat vas deferens. Recordings from C-fibres in arthritic joints revealed an enhanced resting discharge, a greater number of receptive fields and lower mechanical activation thresholds (sensitisation) of mechanonociceptors as compared to untreated joints. Indomethacin significantly attenuated, but did not abolish, either the elevated resting discharges recorded from C-fibres in arthritic joints or the swelling, mechanical hyperalgesia and inflammation associated with functional studies in monoarthric rats. The results show that C-fibre afferent discharge from articular mechanonociceptors in the normal and chronically-inflamed (adjuvant-arthritic) rat ankle joint is modulated by bradykinin (excitation and sensitisation). Catecholamines can also cause excitation and sensitisation of arthritic joints, but purines appear to have no effect on the activity of these sensory receptors. Bradykinin, acting via bradykinin B₂ receptors plays an important role in altering neural excitability in the rat, and different subtypes of B₂ receptor may be involved. Overall, the present results add further to our knowledge and understanding of the peripheral mechanisms involved in nociception in the normal state and in chronic inflammation.

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Yasuyoshi, Hiroki. "Protective Effect of Bradykinin Against Glutamate Neurotoxicity in Cultured Rat Retinal Neurons." Kyoto University, 2000. http://hdl.handle.net/2433/180887.

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Vincent, Karla Kristine. "Transactivation of Beta 2 Adrenergic Receptor by Bradykinin type 2 Receptor via heterodimerization." Diss., Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/37117.

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Although a long standing convention maintained that G Protein Coupled Receptors (GPCRs) exist in the plasma membrane solely as monomers, substantial work over the last two decades has demonstrated that these ubiquitous receptors can and in many cases, preferentially, exist as homodimers, heterodimers, or higher order oligomers. Often, two GPCRs of the same class heterodimerize; it is less common for two GPCRs of different signaling pathways to interact. The work presented here studied the physical and functional interaction of two GPCRs from discrete classes, the Beta 2 Adrenergic Receptor (β2AR), a Gαs-coupled receptor, and Bradykinin type 2 Receptor (Bk2R), a Gαq coupled receptor. These data show that Bk2R and β2AR are physically coupled when heterologously expressed in Xenopus oocytes, and in pheochromocytoma (PC12) cells and in freshly isolated murine ventricular myocytes, two systems that endogenously express these receptors. This physical coupling led to functional consequences in heterologous and endogenous expression systems, as Bk2R was able to transactivate β2AR signaling via its direct interaction with the receptor. Furthermore, coexpression of Bk2R shifted the dose response curve of β2AR for its selective agonist rightward in Xenopus oocyte electrophysiology experiments, suggesting the presence of Bk2R negatively affected β2AR native pharmacology. Up to thirty minutes of either bradykinin (BK) or isoproterenol exposure did not change the relative amount of Bk2R/β2AR heterodimer in PC12 cells, a rat adrenal medulla tumor cell line that endogenously expresses these receptors. Despite the obvious signaling consequences, the Bk2R/β2AR heterodimer accounted for only 10% of the total β2AR protein detected and 20% of the total Bk2R protein detected. When other Bk2R-specific ligands were also tested to examine the extent of β2AR transactivation, our data showed that both Lys-des-Arg-Bradykinin, a Bk2R partial agonist and NPC 567, a Bk2R antagonist, transactivated β2AR to the same extent as BK. Taken together, our data provide a novel mode of receptor regulation and signaling via Bk2R/β2AR heterodimerization. Because a large percentage of therapeutics target GPCRs, a greater understanding of how a GPCR heterodimer functions could be beneficial for targeting new drugs and refining existing drugs. Understanding the Bk2R/β2AR heterodimer provides a new perspective on the myriad of fucntional consequences that occur when a GPCR is activated.

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Lehmberg, Jens Matthias. "Die Mediatorfunktion von Bradykinin und Platelet-Activating Factor bei der globalen zerebralen Ischämie." Diss., lmu, 2002. http://nbn-resolving.de/urn:nbn:de:bvb:19-7775.

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Feng, Jun. "The mechanism of ischemic preconditionning in rat heart, implications of norepinephrine and bradykinin." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ32626.pdf.

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Ellard, John. "Studies towards the synthesis of L-755,807 : a novel, non-peptide bradykinin antagonist." Thesis, University of Warwick, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341597.

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Miao, Kai. "Microcirculation: Electrophysiological Basis for the Response of Endothelial Cells to Inflammatory Mediators-bradykinin." Digital Commons @ East Tennessee State University, 1994. https://dc.etsu.edu/etd/2749.

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Using conventional microelectrodes, I studied the electrical basis for determining the resting V$\sb{\rm m}$ in intact EC's from hamsters. The resting V$\sb{\rm m}$ were found to be $-$40 mV for aortic EC's and $-$43 mV for vena caval EC's. The contributions of ions to the resting V$\sb{\rm m}$ of aortic EC's were compared in terms of the transference number (t$\sb{\rm ion}$). To develop a technique for in situ monitoring changes in V$\sb{\rm m}$ of postcapillary venular EC's in the hamster mesentery, a voltage-sensitive fluorescent probe, bisoxonol, was used to load the cells and the fluorescence signals were analyzed under an intravital microscope by recording the fluorescence intensity (I$\sb{\rm f}$) and processing fluorescent images of the bisoxonol-loaded cells. Calibrations were conducted by simultaneously measuring changes in V$\sb{\rm m}$ with microelectrodes and bisoxonol from aortic EC's and by varying extracellular Na$\sp{+}$ in microvessels. Both calibrations yielded the linear relationship between V$\sb{\rm m}$ and bisoxonol I$\sb{\rm f}$, showing the slope of 5.7%/mV for aortic EC's and 5.2%/mV for microvascular EC's. Altering extracellular K$\sp{+}$ to 25, 50, and 100 mM in the suffusate depolarized microvascular EC's by 5, 8, and 10 mV; whereas, the same alterations via both suffusion and perfusion induced the depolarization by 18, 30, and 42 mV, indicating that the K$\sp{+}$ conductance has an asymmetric distribution. Ba$\sp{2+}$ (1 mM) produced a depolarization by 70 mV, suggesting that the activity of K$\sp{+}$ channels dominates the resting V$\sb{\rm m}$. To correlate the bradykinin-induced increase in microvascular permeability to the changes in V$\sb{\rm m}$, the albumin flux (J$\sb{\rm A}$) was measured using TRITC-albumin along with monitoring V$\sb{\rm m}$. Bradykinin(l $\mu$M) induced a hyperpolarization of EC's by 8 mV and a biphasic increase in J$\sb{\rm A}$ from the basal level of 1.00 x 10$\sp{-6}$ to a transient peak of 9.17 x 10$\sp{-6}$ followed by a sustained level of 3.05 x 10$\sp{-6}$ cm/s. The linear correlations of net increases in both the peak and the sustained values of J$\sb{\rm A}$ to changes in V$\sb{\rm m}$ indicate that the hyperpolarization determines the peak in part and the sustained level in all. Under high K$\sp{+}$ (50 mM), bradykinin produced a repolarization from a depolarized V$\sb{\rm m}$ of -54 mV to -66 mV and a smaller increase in J$\sb{\rm A}$ from the basal level of 0.38 x 10$\sp{-6}$ to the peak of 5.51 x 10$\sp{-6}$ followed by a significantly lowered, sustained level of 1.11 x 10$\sp{-6}$ cm/s. The repolarization under high K$\sp{+}$ indicates that besides the activation of Ca$\sp{2+}$-dependent K$\sp{+}$ channels, other electrical events may be implicated. The correlation between the repolarization and the lowered value of J$\sb{\rm A}$ at the peak implies that this variation in V$\sb{\rm m}$ also mediates the bradykinin-induced increase in J$\sb{\rm A}$ under high K$\sp{+}$ condition. (Abstract shortened by UMI.)

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Shao, Xiuping. "The effects of bradykinin and angiotensin II on the thoracic aorta vasa sasorum microcirculation system." Mémoire, Sherbrooke : Université de Sherbrooke, 2001. http://savoirs.usherbrooke.ca/handle/11143/3236.

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Parsopoulou, Faidra. "Biomarqueurs pronostiques et prédictifs de la sévérité de l'angioedème héréditaire." Thesis, Université Grenoble Alpes, 2020. http://www.theses.fr/2020GRALV041.

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L’expression clinique de l’angioedème héréditaire C1-INH-AOH est hétérogène. L'identification de biomarqueurs et la disponibilité de tests biologiques pourraient rendre compte de cette observation. Ainsi, notre travail a retenu quatre points:I. L'expression des récepteurs de la bradykinine. Les récepteurs B1 et B2 sont des cibles thérapeutiques potentielles. Par les ligands fluorescents spécifiques pour B1 et B2, nous avons cherché à quantifier les récepteurs pour leur expression sur les lignées EA.hy926 et THP1, pour examiner l’expression sur les cellules endothéliales des patients en condition de repos ou en période symptomatique. L’expression spontanée des récepteurs n'a pu être quantifiée par faible expression ou faible affinité des ligands. Des recherches supplémentaires sont nécessaires pour développer un outil de diagnostic et procéder à des examens sur les échantillons humains.II. Activation du variant p.Lys330Glu du plasminogène. Le variant a été précédemment décrit comme pathogène pour l’angioedème héréditaire HAE-PLG. Examiné chez des porteurs hétérozygotes et homozygotes, le variant p.Lys330Glu se présente avec une modification de la glycosylation du plasminogène, avec une inversion du modèle de glycosylation chez le porteur homozygote et deux bandes d'intensité égale pour les porteurs hétérozygotes. Le variant p.Lys330Glu présente une sensibilité significativement élevée à l'activation par la streptokinase et l’urokinase, par mesure enzymatique à l’aide d’un chromogène spécifique à la plasmine. L'impact du variant p.Lys330Glu provoque une augmentation de la transformation du plasminogène en plasmine, avec une production de BK par activation du système kallicréine-kinine.III. Association de variants génétiques à la sévérité de l’angioedème C1-INH-AOH. La combinaison de variants sur des gènes codant pour des protéines impliquées dans le métabolisme et la fonction de la bradykinine peut modifier chez le porteur l'expression clinique de l’angioedème C1-INH-AOH. Par la technologie NGS, des variants rares (MAF≤1%) ont été recherchés dans 54 gènes pour être identifiés dans des combinaisons avec SERPING1. 18 polymorphismes fonctionnels ont été retenus (MAF≥1%) et s’associent à l'âge de l'apparition de la maladie, au score de sévérité et au besoin d’une prophylaxie, quel que soit le variant SERPING1 combiné ou chez les porteurs d'un faux-sens de SERPING1. Concernant les variants fonctionnels communs et indépendamment du variant SERPING1, les porteurs de l’allèle C de F12-rs1801020 présentent une sévérité de la maladie augmentée; la présence du SERPING1-rs28362944 multiplient par 2,5 la probabilité d’un besoin de prophylaxie; SERPING1-rs4926 a été associé à un retard de l'âge de l'apparition des symptômes; F13B-rs6003, SERPINA1-rs28929474 et PLAU-rs2227564 ont été associés à la sévérité de C1-INH-AOH. Pour les porteurs d'un variant faux-sens de SERPING1, les porteurs de l’allèle C de F12-rs1801020 présentent de la sévérité augmentée; la présence du SERPING1-rs28362944 multiplient par 4,2 la probabilité d’un besoin de prophylaxie; SERPINA1-rs17580 et SERPINE1-rs6092 ont été associés à l'âge de l'apparition des symptômes; l'hétérozygotie pour CPN1-rs61751507 est indépendamment associée à une diminution de 98% du besoin de prophylaxie; F2-rs1799963 a été associé à la sévérité de la maladie. Enfin, KLKB1-rs3733402 et KLK1-rs5515 ont été associés à l'âge de l'apparition des symptômes et à la sévérité. Ce premier examen des gènes devrait être poursuivi pour conclure sur la contribution à la maladie des variants rares détectés, leurs fonctions et leur validité clinique.IV. Partage des données au niveau mondial. Nous avons classé et soumis dans la base de données ClinVar 45 variantes de SERPING1 précédemment détectées chez des patients de C1-INH-AOH du Laboratoire d'immunologie et d'Histocompatibilité de l'UTH, accompagnées des preuves cliniques
The heterogeneous clinical manifestations and the unpredictable nature of C1-INH-HAE require the identification of biomarkers and the development of accompanying bioassays. To contribute to this purpose this thesis focused on four topics:I. The expression of bradykinin receptors. B1R and B2R are potential therapeutic targets. Molecular imaging agents enable the visualization and quantification of the receptors at a cellular level. Specific fluorescent ligands were prepared and used as imaging agents in order to examine the expression of the receptors on EA.hy926 and THP1 cell lines and subsequently, on the surface of patients’ endothelial cells in resting conditions or during an attack. The detection of naturally expressed receptors was not successful due to low expression or due to low affinity of the ligands. Further investigation is required to develop a diagnostic tool and proceed in human blood samples.II. Activation of PLG with p.Lys330Glu variant. The alteration of PLG glycosylation patterns was examined in heterozygous and homozygous carriers of PLG p.Lys330Glu variant, previously described as pathogenic for HAE-PLG. In the homozygous patient, a reversal of the glycosylation pattern was observed, while the heterozygous subjects presented the two glycoforms at the same level. A plasmin-specific chromogenic assay was developed in order to measure the PLG susceptibility to activation. Both homozygous and heterozygous carriers displayed a significantly high susceptibility to activation by streptokinase and urokinase. The qualitative in vivo impact of p.Lys330Glu on the protein may result in increased plasmin formation and excessive bradykinin production through kallikrein-kinin system activation.III. Association of genetic variants with the severity of C1-INH-HAE. The concomitant carriage of variants on genes encoding for proteins involved in bradykinin metabolism and function may modify the clinical expression of C1-INH-HAE. Using NGS technology the study aimed to detect and classify rare variants (MAF≤1%) in 54 genes other than SERPING1 and to associate the carriage of 18 selected functional SNPs (MAF≥1%) with C1-INH-HAE patients’ age at disease onset, disease severity based on CALS score and need for LTP, regardless the SERPING1 mutational status and separately in patients carrying a missense SERPING1 variant. In the first group of patients, the presence of the C allele of F12-rs1801020 was significantly associated with an increase at disease severity; the presence of SERPING1-rs28362944 increased 2.5-fold the probability of LTP need; SERPING1-rs4926 was associated with later disease onset; F13B-rs6003, SERPINA1-rs28929474 and PLAU-rs2227564 were significantly associated with the severity of the disease. In carriers of a missense SERPING1 mutation, the presence of the C allele of F12-rs1801020 was significantly associated with an increase at disease severity; the presence of SERPING1-rs28362944 increased 4.2-fold the probability of LTP need; SERPINA1-rs17580 and SERPINE1-rs6092 were significantly associated with earlier and later age at disease onset, respectively; CPN1-rs61751507 and F2-rs1799963 were significantly associated with decrease of need for LTP and disease severity, respectively; KLKB1-rs3733402 and KLK1-rs5515 were associated with both the age at disease onset and the disease severity. Further analyses should be done in order to conclude on the contribution of the detected rare variants to the disease, their functional effects and their clinical validity.IV. Global data sharing. In order for both researchers and physicians to assess the available genetic data, they need to be classified and shared in public, user-friendly, easily accessible databases. To this aim, we classified and submitted in ClinVar database 45 SERPING1 variants previously detected in C1-INH-HAE patients of the Laboratory of Immunology and Histocompatibility of the UTH, accompanied by the supporting clinical evidence

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47

Schulz, Joachim. "Die therapeutische Wirkung eines neuen Bradykinin B2- Rezeptorantagonisten - LF160687 MS - auf das vasogene Hirnödem." Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-44107.

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48

Kläsner, Benjamin. "Antagonisierung von Bradykinin-B2-Rezeptoren nach fokaler zerebraler Ischämie - Therapeutisches Fenster bei der Ratte." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-61084.

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49

Hosogi, Miwa. "Bradykinin is a potent pruritogen in atopic dermatitis : a switch from pain to itch." Kyoto University, 2007. http://hdl.handle.net/2433/135696.

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Schweinberger, Anna. "Einfluss zyklischer mechanischer Dehnung auf das Kinin-Kallikrein-System in alveolären Typ-II-Zellen der Ratte." Doctoral thesis, Universitätsbibliothek Leipzig, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-219314.

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Beatmungsbedingte Lungenschäden in der Therapie des akuten Atemnotsyndroms (ARDS) sind aufgrund der inhomogenen Vorschädigung der Lunge praktisch unvermeidbar. Die unphysiologische mechanische Belastung der Lunge führt über Volutrauma, Atelektotrauma und Biotrauma nicht selten zur Exazerbation des Syndroms und trägt zur hohen Mortalität des ARDS bei. Pharmakologische Interventionsmöglichkeiten sind Gegenstand der aktuellen Forschung. Diesbezüglich vielversprechend ist die zentrale Komponente des Kinin-Kallikrein-Systems, namentlich Bradykinin, das über seinen B2-Rezeptor anti-apoptotische Signalwege aktivieren kann und somit zellprotektive Wirkung besitzt. In der vorliegenden Arbeit wurde untersucht, in welcher Weise zyklische mechanische Dehnung die Konzentration einzelner Komponenten des Kinin-Kallikrein-Systems in isolierten alveolären Epithelzellen (Typ II) der Ratte beeinflusst. Dafür wurden die alveolären Typ-II-Zellen auf speziellen BioFlex®-Membranen kultiviert und für 24 Stunden zyklisch mit hoher Dehnungsamplitude gedehnt. Anschließend wurden mit etablierten Analysemethoden in Zellüberständen bzw. Zelllysaten die Konzentrationen von Kininogen 1, Bradykinin und vom B2-Rezeptor gemessen, sowie die Aktivität des Enzyms Kallikrein und des Bradykinin-Abbaus bestimmt - jeweils im Vergleich mit Überständen bzw. Lysaten ungedehnter AT-II-Zellkulturen. Es zeigte sich dehnungs-bedingt eine Zunahme der Bradykinin-Produktion durch Kininogen und Kallikrein und eine stark gesteigerte Bradykinin-abbauende Aktivität, sodass sich der Bradykininspiegel insgesamt verringerte. Die Konzentration des B2-Rezeptors blieb unverändert. Detailliertes Wissen über den Einfluss zyklischer mechanischer Dehnung auf die Einzelkomponenten des Kinin-Kallikrein-Systems ist eine Grundvoraussetzung, um die zellprotektive Wirkung von Bradykinin im Sinne einer pharmakologischen Interventionsmöglichkeit bei ARDS nutzbar machen zu können.

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Dissertations / Theses on the topic 'Bradykinin'

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