Kinin-B1 Receptors in Ischaemia-Induced Pancreatitis: Functional Importance and Cellular Localisation

Kuebler, Joachim F.; Schremmer-Danninger, Elisabeth; Bhoola, K. D.; Roscher, Adelbert A.; Meßmer, K.; Hoffmann, T.

doi:10.1515/bc.2003.147

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…[52][53][54] Activation of the kinin-kallikrein system is observed in pancreatitis and causes the vascular effects associated with the disease. 55,56 Inhibition of bradykinin action is used as a mode of therapy for pancreatitis patients. [56][57][58][59][60] Vitronectin is also consistent with hemolysis and pancreatitis because of its role as a complement and cytolysis inhibitor.…”

Section: Discussionmentioning

confidence: 99%

“…55,56 Inhibition of bradykinin action is used as a mode of therapy for pancreatitis patients. [56][57][58][59][60] Vitronectin is also consistent with hemolysis and pancreatitis because of its role as a complement and cytolysis inhibitor. 61,62 Each of these proteins plays a role in pancreatic inflammation and the corresponding host response.…”

Section: Discussionmentioning

confidence: 99%

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Diagnostic protein discovery using proteolytic peptide targeting and identification

Koomen

Zhao

et al. 2004

Rapid Comm Mass Spectrometry

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Plasma protein profiling with mass spectrometry is currently being evaluated as a diagnostic tool for cancer and other diseases. These experiments consist of three steps: plasma protein fractionation, analysis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), and comparisons of the MALDI profiles to develop diagnostic fingerprints using bioinformatic techniques. While preliminary results appear promising in small sample groups, the method is limited by the sensitivity of MALDI-MS for intact proteins, the limited mass range of MALDI-MS, and difficulties associated with isolating individual proteins for identification to validate the diagnostic fingerprint. Here we present an alternative and improved method directed toward diagnostic protein discovery, which incorporates proteolytic peptide profiling, bioinformatic targeting of ion signals, and MALDI tandem mass spectrometry (MS/MS) peptide sequencing, rather than fingerprinting. Pancreatic cancer patients, pancreatitis patients, and controls are used as the model system. Profiling peptides after enzymatic digestion improves sensitivity and extends the accessible protein molecular weight range when compared to intact protein profiling. The first step is to extract and fractionate the proteins from plasma. Each fraction is digested with trypsin and subsequently analyzed by MALDI-MS. Rather than using bioinformatic analysis as a pattern-matching technique, peptides are targeted based on the disease to control peak intensity ratios measured in the averages of all mass spectra in each group and t-tests of the intensity of each individual peak. The targeted peptide ion signals are subsequently identified using MALDI-MS/MS in quadrupole-TOF and tandem-TOF instruments. This study found not only the proteins targeted and identified by a previous protein profiling experiment, but also detected additional proteins. These initial results are consistent with the known biology of pancreatic cancer or pancreatitis, but are not specific to those diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Diagnostic protein discovery using proteolytic peptide targeting and identification

Koomen

Zhao

et al. 2004

Rapid Comm Mass Spectrometry

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“…In mice, either pharmacological blocking with selective B 1 antagonist [Leu 8 ]‐des‐Arg 9 ‐BK or gene deletion of B 1 receptors largely diminishes the infarction's extension, an effect that further reinforces the relevance of B 1 receptors under these conditions. Kuebler et al . (2003) have affirmed that B 1 receptors also seem relevant in the ischaemia–reperfusion of rat pancreas.…”

Section: The B1 Receptor and Its Role In Development And Maintenance mentioning

confidence: 99%

“…The authors have demonstrated, by means of binding studies, that B 1 receptor expression is augmented by about 22‐fold after pancreatic ischaemia–reperfusion injury. They have also shown that the B 1 receptor antagonist CP‐0298 (alone or in combination with the B 2 antagonist CP‐0597) significantly reduces the number of adherent leukocytes in postcapillary venules ( Kuebler et al ., 2003 ). Another recent contribution has demonstrated that intestinal ischaemia–reperfusion injury results in a striking increase of B 1 receptor expression in rats ( Souza et al ., 2004 ).…”

Section: The B1 Receptor and Its Role In Development And Maintenance mentioning

confidence: 99%

Kinin B₁ receptors: key G‐protein‐coupled receptors and their role in inflammatory and painful processes

Calixto

Medeiros

Fernandes

et al. 2004

British J Pharmacology

239

201

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Kinins are a family of peptides implicated in several pathophysiological events. Most of their effects are likely mediated by the activation of two G-protein-coupled receptors: B 1 and B 2 . Whereas B 2 receptors are constitutive entities, B 1 receptors behave as key inducible molecules that may be upregulated under some special circumstances. In this context, several recent reports have investigated the importance of B 1 receptor activation in certain disease models. Furthermore, research on B 1 receptors in the last years has been mainly focused in determining the mechanisms and pathways involved in the process of induction. This was essentially favoured by the advances obtained in molecular biology studies, as well as in the design of selective and stable peptide and nonpeptide kinin B 1 receptor antagonists. Likewise, development of kinin B 1 receptor knockout mice greatly helped to extend the evidence about the relevance of B 1 receptors during pathological states. In the present review, we attempted to remark the main advances achieved in the last 5 years about the participation of kinin B 1 receptors in painful and inflammatory disorders. We have also aimed to point out some groups of chronic diseases, such as diabetes, arthritis, cancer or neuropathic pain, in which the strategic development of nonpeptidic oral-available and selective B 1 receptor antagonists could have a potential relevant therapeutic interest.

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“…Much evidence suggests that the integrity of vascular endothelium is an important factor for the development and maintenance of pancreatic islet function (Konstantinova and Lammert, 2004). Accordingly, the expression of kinin B 1 receptor has been described in pancreas (Chai et al, 1996) and it has been demonstrated that this receptor mediates leukocyte adherence in capillary venules in pancreatic vessels (Kuebler et al, 2003) and controls plasma extravasation in pancreatitis in streptozotocintreated mice (Simard et al, 2002;Lawson et al, 2005). Recently, we generated and characterized kinin B 1 receptor knockout mice (B 1 -/-), which were shown to be fertile, normotensive, hypoalgesic and less responsive to lipopolysaccharide (LPS)-induced hypotension (Pesquero et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Role of the kinin B1 receptor in insulin homeostasis and pancreatic islet function

Araújo

Mori

Merino

et al. 2006

Biological Chemistry

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Kinins are potent vasoactive peptides generated in blood and tissues by the kallikrein serine proteases. Two distinct kinin receptors have been described, one constitutive (subtype B2) and one inducible (subtype B1), and many physiological functions have been attributed to these receptors, including glucose homeostasis and control of vascular permeability. In this study we show that mice lacking the kinin B1 receptor (B1-/- mice) have lower fasting plasma glucose concentrations but exhibit higher glycemia after feeding when compared to wild-type mice. B1-/- mice also present pancreas abnormalities, characterized by fewer pancreatic islets and lower insulin content, which leads to hypoinsulinemia and reduced insulin release after a glucose load. Nevertheless, an insulin tolerance test indicated higher sensitivity in B1-/- mice. In line with this phenotype, pancreatic vascular permeability was shown to be reduced in B1 receptor-ablated mice. The B1 agonist desArg9bradykinin injected intravenously can induce the release of insulin into serum, and this effect was not observed in the B1-/- mice or in isolated islets. Our data demonstrate the importance of the kinin B1 receptor in the control of pancreatic vascular homeostasis and insulin release, highlighting a new role for this receptor in the pathogenesis of diabetes and related diseases.

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Kinin-B1 Receptors in Ischaemia-Induced Pancreatitis: Functional Importance and Cellular Localisation

Cited by 8 publications

References 32 publications

Diagnostic protein discovery using proteolytic peptide targeting and identification

Diagnostic protein discovery using proteolytic peptide targeting and identification

Kinin B₁ receptors: key G‐protein‐coupled receptors and their role in inflammatory and painful processes

Role of the kinin B1 receptor in insulin homeostasis and pancreatic islet function

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Kinin-B1 Receptors in Ischaemia-Induced Pancreatitis: Functional Importance and Cellular Localisation

Cited by 8 publications

References 32 publications

Diagnostic protein discovery using proteolytic peptide targeting and identification

Diagnostic protein discovery using proteolytic peptide targeting and identification

Kinin B1 receptors: key G‐protein‐coupled receptors and their role in inflammatory and painful processes

Role of the kinin B1 receptor in insulin homeostasis and pancreatic islet function

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Product

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Kinin B₁ receptors: key G‐protein‐coupled receptors and their role in inflammatory and painful processes