The Experts below are selected from a list of 156 Experts worldwide ranked by ideXlab platform
Stephen Townley Holgate - One of the best experts on this subject based on the ideXlab platform.
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Skin responses to bradykinin, Kallidin, and [desArg9]-bradykinin in nonatopic and atopic volunteers
The Journal of Allergy and Clinical Immunology, 1993Co-Authors: Riccardo Polosa, K Rajakulasingam, Filippo Palermo, Ratko Djukanovic, Stephen Townley HolgateAbstract:Abstract Background: Kinins are potent vasoactive oligopeptides that may act as mediators in a variety of inflammatory diseases of the skin by interacting with specific receptors designated B 1 and B 2 In this study we have investigated the structure-activity relationship of intradermally injected bradykinin, Kallidin (lysine-bradykinin), and [desArg 9 ]-bradykinin in atopic ( n = 8) and nonatopic ( n = 8) subjects. Methods: On two separate occasions, each separated by a week, subjects randomly underwent intradermal challenge with incremental doses (0.5, 5, and 50 nmol) of either the B 1 -agonist [desArg 9 ]-bradykinin, the B 2 -agonists bradykinin or Kallidin, or vehicle placebo. In a separate randomized double-blind study we have also examined the effect of an orally administered antihistamine, terfenadine, on kinin-induced wheat and flare responses and their repeatability in a group of nine volunteers. The skin responses were monitored objectively by measurement of wheal and flare areas. Results: Both bradykinin and Kallidin induced a dose-dependent increase in wheal and flare areas in all subjects studied. Although the effects of the two lowest doses (0.5 and 5 nmol) of [desArg 9 ]-bradykinin on skin responses were indistinguishable from those of placebo, this kinin at the highest dose administered (50 nmol) caused a significant increase in wheal and flare areas in all subjects studied. No difference could be identified in the skin responses to kinins between atopic and nonatopic subjects. In addition kinin-induced cutaneous responses were not altered by pretreatment with terfenadine. Conclusions: These in vivo structure activity studies suggest that in human beings the skin responses to kinins may be compatible with the stimulation of B 2 receptors, which is unrelated to histamine release from cutaneous mast cells.
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Cross-tachyphylactic airway response to inhaled bradykinin, Kallidin and [desArg9]-bradykinin in asthmatic subjects.
European Respiratory Journal, 1993Co-Authors: Riccardo Polosa, Giorgio Prosperini, Lv Milazzo, G. Santonocito, K Rajakulasingam, Stephen Townley HolgateAbstract:Kinins are oligopeptides that may act as mediators in the pathogenesis of bronchial asthma by interacting with specific cell surface receptors designated B1 and B2. When administered by inhalation to asthmatic subjects, bradykinin and Kallidin, but not [desArg9]-bradykinin, provoke potent bronchoconstriction, thus suggesting a specific effect compatible with the stimulation of B2 receptors. To characterize further the receptor(s) mediating this bronchospastic response we have carried out cross-tachyphylactic studies with inhaled bradykinin, Kallidin, and [desArg9]-bradykinin, administered in a randomized double-blind fashion in a group of 10 asthmatic subjects. Inhalation of bradykinin and Kallidin, but not [desArg9]-bradykinin, elicited concentration-related falls in forced expiratory volume in one second (FEV1) in all the subjects studied. The geometric mean provocation concentrations of inhaled agonists reducing FEV1 by 20% of baseline (PC20) were 0.12 and 0.28 mg.ml-1 for bradykinin and Kallidin, respectively. When inhaled at concentrations up to 10.62 mg.ml-1, [desArg9]-bradykinin failed to provoke any significant fall in FEV1 from baseline in any of the subjects studied. Following recovery from the second bradykinin challenge, provocation with Kallidin revealed a reduced response to this agonist, the PC20 value increasing from 0.28 to 1.23 mg.ml-1. Similarly, once the airways had recovered from the second Kallidin challenge, provocation with bradykinin also showed a reduced response, the PC20Bk increasing from 0.12 to 0.94 mg.ml-1. Surprisingly, despite failing to cause bronchoconstriction, repeated exposures with inhaled [desArg9]-bradykinin reduced the airway response to bradykinin, the PC20Bk increasing from 0.12 to 0.41 mg.ml-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Riccardo Polosa - One of the best experts on this subject based on the ideXlab platform.
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Skin responses to bradykinin, Kallidin, and [desArg9]-bradykinin in nonatopic and atopic volunteers
The Journal of Allergy and Clinical Immunology, 1993Co-Authors: Riccardo Polosa, K Rajakulasingam, Filippo Palermo, Ratko Djukanovic, Stephen Townley HolgateAbstract:Abstract Background: Kinins are potent vasoactive oligopeptides that may act as mediators in a variety of inflammatory diseases of the skin by interacting with specific receptors designated B 1 and B 2 In this study we have investigated the structure-activity relationship of intradermally injected bradykinin, Kallidin (lysine-bradykinin), and [desArg 9 ]-bradykinin in atopic ( n = 8) and nonatopic ( n = 8) subjects. Methods: On two separate occasions, each separated by a week, subjects randomly underwent intradermal challenge with incremental doses (0.5, 5, and 50 nmol) of either the B 1 -agonist [desArg 9 ]-bradykinin, the B 2 -agonists bradykinin or Kallidin, or vehicle placebo. In a separate randomized double-blind study we have also examined the effect of an orally administered antihistamine, terfenadine, on kinin-induced wheat and flare responses and their repeatability in a group of nine volunteers. The skin responses were monitored objectively by measurement of wheal and flare areas. Results: Both bradykinin and Kallidin induced a dose-dependent increase in wheal and flare areas in all subjects studied. Although the effects of the two lowest doses (0.5 and 5 nmol) of [desArg 9 ]-bradykinin on skin responses were indistinguishable from those of placebo, this kinin at the highest dose administered (50 nmol) caused a significant increase in wheal and flare areas in all subjects studied. No difference could be identified in the skin responses to kinins between atopic and nonatopic subjects. In addition kinin-induced cutaneous responses were not altered by pretreatment with terfenadine. Conclusions: These in vivo structure activity studies suggest that in human beings the skin responses to kinins may be compatible with the stimulation of B 2 receptors, which is unrelated to histamine release from cutaneous mast cells.
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Cross-tachyphylactic airway response to inhaled bradykinin, Kallidin and [desArg9]-bradykinin in asthmatic subjects.
European Respiratory Journal, 1993Co-Authors: Riccardo Polosa, Giorgio Prosperini, Lv Milazzo, G. Santonocito, K Rajakulasingam, Stephen Townley HolgateAbstract:Kinins are oligopeptides that may act as mediators in the pathogenesis of bronchial asthma by interacting with specific cell surface receptors designated B1 and B2. When administered by inhalation to asthmatic subjects, bradykinin and Kallidin, but not [desArg9]-bradykinin, provoke potent bronchoconstriction, thus suggesting a specific effect compatible with the stimulation of B2 receptors. To characterize further the receptor(s) mediating this bronchospastic response we have carried out cross-tachyphylactic studies with inhaled bradykinin, Kallidin, and [desArg9]-bradykinin, administered in a randomized double-blind fashion in a group of 10 asthmatic subjects. Inhalation of bradykinin and Kallidin, but not [desArg9]-bradykinin, elicited concentration-related falls in forced expiratory volume in one second (FEV1) in all the subjects studied. The geometric mean provocation concentrations of inhaled agonists reducing FEV1 by 20% of baseline (PC20) were 0.12 and 0.28 mg.ml-1 for bradykinin and Kallidin, respectively. When inhaled at concentrations up to 10.62 mg.ml-1, [desArg9]-bradykinin failed to provoke any significant fall in FEV1 from baseline in any of the subjects studied. Following recovery from the second bradykinin challenge, provocation with Kallidin revealed a reduced response to this agonist, the PC20 value increasing from 0.28 to 1.23 mg.ml-1. Similarly, once the airways had recovered from the second Kallidin challenge, provocation with bradykinin also showed a reduced response, the PC20Bk increasing from 0.12 to 0.94 mg.ml-1. Surprisingly, despite failing to cause bronchoconstriction, repeated exposures with inhaled [desArg9]-bradykinin reduced the airway response to bradykinin, the PC20Bk increasing from 0.12 to 0.41 mg.ml-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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Comparative nasal effects of bradykinin, Kallidin and [Des-Arg9]-bradykinin in atopic rhinitic and normal volunteers.
The Journal of physiology, 1991Co-Authors: K Rajakulasingam, Riccardo Polosa, S. T. Holgate, Peter H. HowarthAbstract:1. The structure-activity relationship of kinins within the nose has been investigated in atopic rhinitic (n = 7) and non-rhinitic (n = 7) subjects. On 4 separate days, each separated by a week, subjects randomly underwent nasal challenge with incremental doses of either the B1 agonist [Des-Arg9]-bradykinin, the B2 agonists Kallidin or bradykinin, or vehicle placebo in a double-blind comparative study. The nasal response was monitored objectively by measurement of nasal airways resistance (NAR) by active posterior rhinomanometry and subjectively by symptom reporting of nasal blockage, rhinorrhoea, nasal itch and nasal pain. 2. The B2 agonists Kallidin and bradykinin both induced a dose-dependent increase in NAR (P less than 0.001) and were associated with symptomatic reporting of nasal blockage (P less than 0.05), rhinorrhoea (P less than 0.01) and nasal discomfort (P less than 0.05) compared to placebo. In contrast the effects of the B1 agonist [Des-Arg9]-bradykinin on NAR and symptom reporting were indistinguishable from placebo. No difference could be identified in the nasal response to Kallidin and bradykinin between rhinitic and non-rhinitic subjects and there was no evidence of B1 receptor upregulation in the disease state. For the whole group the provocative dose of agonist inducing a 50% increase in NAR (PD50) was 1.77 x 10(-4) mol for bradykinin and 2.86 x 10(-4) mol for Kallidin (P greater than 0.05). 3. These findings identify that the nasal effects of kinins are mediated through B2 receptors and the advent of B2 receptor antagonists will permit a further evaluation of the role of kinins in rhinitis.
Ulrich Hilgenfeldt - One of the best experts on this subject based on the ideXlab platform.
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ca2 signalling of kinins in cells expressing rat mouse and human b1 b2 receptor
International Immunopharmacology, 2008Co-Authors: Radka Zubakova, Andreas Gille, Alexander Faussner, Ulrich HilgenfeldtAbstract:With respect to functional aspects, the kallikrein-kinin-system can be divided into a plasma kallikrein-kinin-system and a tissue kallikrein-kinin-system. At least four functional kinin peptides act via two different G-protein-coupled receptors, an inducible B 1 -receptor and a constitutively expressed B 2 -receptor. B 1 R and B 2 R couple to G q/11 and lead via phospholipase C to Ca 2+ mobilization. In humans both, bradykinin and Kallidin are agonists on the B 2 -receptor. In contrast, bradykinin is believed to be the only kinin acting on the B 2 R in rats and mice. However, recently we have isolated a Kallidin-like-peptide from plasma and urine of rats. Until now the kinin ligand-receptor interactions were mainly characterized in binding studies. However, receptor affinity does not inevitably correspond with the intrinsic activity of an agonist. The aim of the present study was to investigate intracellular calcium mobilization to quantify mouse, rat and human B 1 - and B 2 -receptor activation by bradykinin, Kallidin, des-Arg 9 -bradykinin, des-Arg 10 -Kallidin, and of the two novel rat kinins, Kallidin-like-peptide and des-Arg 10 -Kallidin-like-peptide. In cells stably expressing the human, rat, and mouse B 2 -receptor, respectively, bradykinin, Kallidin, and Kallidin-like-peptide were nearly equipotent (EC 50 , 10 -12 M) at eliciting Ca 2+ -transients. Their des-Arg-derivatives were 103-fold less potent. In cells expressing B 1 -receptor the des-Arg derivatives elicited Ca 2+ -signals at an EC 50 in the order of 10 -9 M. Major differences between these peptides could not be observed. Bradykinin, Kallidin, and Kallidin-like-peptide caused a Ca 2+ -signal at substantially higher concentrations in the order of 10 -7 M. The data show that des-Arg 9 -bradykinin, des-Arg 10 -Kallidin, and des-Arg 10 -Kallidin-like-peptide are equipotent agonists at the B 1 -receptor. Bradykinin, Kallidin and Kallidin-like-peptide are equipotent agonists at the B 2 -receptor.
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Ca2+ signalling of kinins in cells expressing rat, mouse and human B1/B2-receptor.
International immunopharmacology, 2007Co-Authors: Radka Zubakova, Andreas Gille, Alexander Faussner, Ulrich HilgenfeldtAbstract:With respect to functional aspects, the kallikrein-kinin-system can be divided into a plasma kallikrein-kinin-system and a tissue kallikrein-kinin-system. At least four functional kinin peptides act via two different G-protein-coupled receptors, an inducible B1-receptor and a constitutively expressed B2-receptor. B1R and B2R couple to G(q/11) and lead via phospholipase C to Ca2+ mobilization. In humans both, bradykinin and Kallidin are agonists on the B2-receptor. In contrast, bradykinin is believed to be the only kinin acting on the B2R in rats and mice. However, recently we have isolated a Kallidin-like-peptide from plasma and urine of rats. Until now the kinin ligand-receptor interactions were mainly characterized in binding studies. However, receptor affinity does not inevitably correspond with the intrinsic activity of an agonist. The aim of the present study was to investigate intracellular calcium mobilization to quantify mouse, rat and human B1- and B2-receptor activation by bradykinin, Kallidin, des-Arg9-bradykinin, des-Arg10-Kallidin, and of the two novel rat kinins, Kallidin-like-peptide and des-Arg10-Kallidin-like-peptide. In cells stably expressing the human, rat, and mouse B2-receptor, respectively, bradykinin, Kallidin, and Kallidin-like-peptide were nearly equipotent (EC50, 10(-12)M) at eliciting Ca2+-transients. Their des-Arg-derivatives were 10(3)-fold less potent. In cells expressing B1-receptor the des-Arg derivatives elicited Ca2+-signals at an EC50 in the order of 10(-9)M. Major differences between these peptides could not be observed. Bradykinin, Kallidin, and Kallidin-like-peptide caused a Ca2+-signal at substantially higher concentrations in the order of 10(-7)M. The data show that des-Arg9-bradykinin, des-Arg10-Kallidin, and des-Arg10-Kallidin-like-peptide are equipotent agonists at the B1-receptor. Bradykinin, Kallidin and Kallidin-like-peptide are equipotent agonists at the B2-receptor.
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Kallidin-like peptide mediates the cardioprotective effect of the ACE inhibitor captopril against ischaemic reperfusion injury of rat heart
British journal of pharmacology, 2006Co-Authors: Xiuxin Liu, Radka Zubakova, Martina Lukasova, Sabina Lewicka, Ulrich HilgenfeldtAbstract:1 The potential cardioprotective effect of ACE inhibitors has been attributed to the inhibition of bradykinin degradation. Recent data in rats documented a Kallidin-like peptide, which mimics the cardioprotective effect of ischaemic preconditioning. This study investigates in isolated Langendorff rat heart the effect of the ACE inhibitor captopril, the role of bradykinin, Kallidin-like peptide, and nitric oxide (NO). 2 The bradykinin level in the effluent of the control group was 14.6 pg ml−1 and was not affected by captopril in the presence or absence of kinin B2-receptor antagonist, HOE140. 3 The Kallidin-like peptide levels were approximately six-fold higher (89.8 pg ml−1) and increased significantly by treatment with captopril (144 pg ml−1), and simultaneous treatment with captopril and HOE140 (197 pg ml−1). 4 Following 30 min ischaemia in the control group, the creatine kinase activity increased from 0.4 to 53.4 U l−1. In the captopril group and in the captopril+L-NAME group, the creatine kinase activity was significantly lower (18.5 and 22.8 U l−1). This beneficial effect of captopril was completely abolished by the kinin B2-receptor antagonist, HOE140, as well as by the Kallidin antiserum. 5 Perfusion of the hearts with Kallidin before the 30 min ischaemia, but not with bradykinin, yielded an approximately 50% reduction in creatine kinase activity after reperfusion. 6 Pretreatment with L-NAME alone and simultaneously with captopril, and with Kallidin, respectively, suggests a kinin-independent action of NO before the 30 min ischaemia on coronary flow and a kinin-dependent action after ischaemia. 7 These data show that captopril increases Kallidin-like peptide in the effluent. Kallidin-like peptide via kinin B2 receptor seems to be the physiological mediator of cardioprotective actions of captopril against ischaemic reperfusion injury. HOE140 as well as the Kallidin antiserum abolished the cardioprotective effects of captopril. British Journal of Pharmacology (2006) 148, 825–832. doi:10.1038/sj.bjp.0706799
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Rat tissue kallikrein releases a Kallidin-like peptide from rat low-molecular-weight kininogen.
British journal of pharmacology, 2005Co-Authors: Ulrich Hilgenfeldt, Martina Lukasova, Christina Stannek, Martina Schnölzer, Sabina LewickaAbstract:The kallikrein–kinin system is subdivided into the plasma and tissue–kallikrein–kinin system, with bradykinin (BK) and Kallidin (KAL) (Lys0-bradykinin) as functional peptides. This occurs in both humans and other mammals. Both peptides are released by plasma and tissue–kallikrein. BK, but not KAL, has been detected in rats until now. One can explain this observation by the structural differences found in the sequence of rat high- and low-molecular kininogen containing an Arg-residue instead of a Lys-residue in front of the N-terminus of the BK sequence. Nevertheless, we were able to measure a Kallidin-like peptide (KLP), in rat plasma and urine, using a specific KAL antiserum. In order to confirm our data, we isolated low-molecular-weight kininogen from rat plasma and incubated it with purified rat glandular kallikrein. The generated peptide was retained on a high-pressure liquid chromatography column and displaced by an excess of angiotensin I. The KLP-containing fraction was identified with the KLP radioimmunoassay. A specific ion signal with a mass to charge ratio (m/z) of 1216.73 was detected with matrix-assited laser desorption/ionization mass spectrometry. As proposed earlier, the structure of this peptide is Arg1-KAL, instead of Lys1-KAL. The structural similarity between the Lys- and the Arg-residue explains the high crossreactivity (80%) of KLP with the specific KAL antibody. The incubation of KLP with angiotensin-converting enzyme yields two molecules with masses of 913.4 and 729.3 containing the sequence H–Arg–Arg–Pro–Pro–Gly–Phe–Ser–Pro–OH and H–Arg–Arg–Pro–Pro–Gly–Phe–OH. The enzymatic cleavage could be inhibited by captopril. The data suggest that in rats, as in other mammals, the tissue kallikrein–kinin system mediates its physiological effects via a Kallidin-like peptide, which is Arg1-Kallidin (Arg0-bradykinin). British Journal of Pharmacology (2005) 146, 958–963. doi:10.1038/sj.bjp.0706409
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Contraction-related factors affect the concentration of a Kallidin-like peptide in rat muscle tissue.
The Journal of physiology, 2002Co-Authors: Fernando Boix, Ulrich Hilgenfeldt, Laila Rosenborg, Stein KnardahlAbstract:In order to study the effects of the manipulation of various factors related to muscular activity on the concentration of kinins in muscular tissue, a microdialysis probe was implanted in the adductor muscle of the hindlimb in anaesthetized rats. After collection of baseline samples, the perfusion fluid was changed to a Ringer solution containing sodium lactate (10 or 20 mM), adenosine (50 or 100 microM) or a lower pH (7.0 or 6.6). Whereas perfusion with lactate did not have any significant effect on the concentration of kinins in the dialysate, the perfusion with a lower pH or with adenosine dose-dependently increased the kinin content in the samples. In a second microdialysis experiment, by using specific radioimmunoassays (RIA) for bradykinin and Kallidin, we observed that about 70 % of the total kinins dialysed from rat muscle are a Kallidin-like peptide. Also, the simultaneous perfusion with 100 microM caffeine totally abolished the increase in kinin levels induced by the perfusion at pH 6.6. In a third experiment, soleus muscles from rat were stimulated in vitro during 30 min in the presence or absence of 77 microM caffeine. Electrically stimulated contraction, but not the addition of 10 mU ml(-1) insulin, induced an increase in the concentration of the Kallidin-like peptide in the buffer. This effect was totally prevented by the addition of the adenosine antagonist caffeine. These results show that a Kallidin-like peptide is released from rat muscle, and that its production is enhanced by muscle activity. Furthermore, the increase in kinin peptides during muscle contraction may be mediated by an increase in adenosine levels.
K Rajakulasingam - One of the best experts on this subject based on the ideXlab platform.
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Skin responses to bradykinin, Kallidin, and [desArg9]-bradykinin in nonatopic and atopic volunteers
The Journal of Allergy and Clinical Immunology, 1993Co-Authors: Riccardo Polosa, K Rajakulasingam, Filippo Palermo, Ratko Djukanovic, Stephen Townley HolgateAbstract:Abstract Background: Kinins are potent vasoactive oligopeptides that may act as mediators in a variety of inflammatory diseases of the skin by interacting with specific receptors designated B 1 and B 2 In this study we have investigated the structure-activity relationship of intradermally injected bradykinin, Kallidin (lysine-bradykinin), and [desArg 9 ]-bradykinin in atopic ( n = 8) and nonatopic ( n = 8) subjects. Methods: On two separate occasions, each separated by a week, subjects randomly underwent intradermal challenge with incremental doses (0.5, 5, and 50 nmol) of either the B 1 -agonist [desArg 9 ]-bradykinin, the B 2 -agonists bradykinin or Kallidin, or vehicle placebo. In a separate randomized double-blind study we have also examined the effect of an orally administered antihistamine, terfenadine, on kinin-induced wheat and flare responses and their repeatability in a group of nine volunteers. The skin responses were monitored objectively by measurement of wheal and flare areas. Results: Both bradykinin and Kallidin induced a dose-dependent increase in wheal and flare areas in all subjects studied. Although the effects of the two lowest doses (0.5 and 5 nmol) of [desArg 9 ]-bradykinin on skin responses were indistinguishable from those of placebo, this kinin at the highest dose administered (50 nmol) caused a significant increase in wheal and flare areas in all subjects studied. No difference could be identified in the skin responses to kinins between atopic and nonatopic subjects. In addition kinin-induced cutaneous responses were not altered by pretreatment with terfenadine. Conclusions: These in vivo structure activity studies suggest that in human beings the skin responses to kinins may be compatible with the stimulation of B 2 receptors, which is unrelated to histamine release from cutaneous mast cells.
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Cross-tachyphylactic airway response to inhaled bradykinin, Kallidin and [desArg9]-bradykinin in asthmatic subjects.
European Respiratory Journal, 1993Co-Authors: Riccardo Polosa, Giorgio Prosperini, Lv Milazzo, G. Santonocito, K Rajakulasingam, Stephen Townley HolgateAbstract:Kinins are oligopeptides that may act as mediators in the pathogenesis of bronchial asthma by interacting with specific cell surface receptors designated B1 and B2. When administered by inhalation to asthmatic subjects, bradykinin and Kallidin, but not [desArg9]-bradykinin, provoke potent bronchoconstriction, thus suggesting a specific effect compatible with the stimulation of B2 receptors. To characterize further the receptor(s) mediating this bronchospastic response we have carried out cross-tachyphylactic studies with inhaled bradykinin, Kallidin, and [desArg9]-bradykinin, administered in a randomized double-blind fashion in a group of 10 asthmatic subjects. Inhalation of bradykinin and Kallidin, but not [desArg9]-bradykinin, elicited concentration-related falls in forced expiratory volume in one second (FEV1) in all the subjects studied. The geometric mean provocation concentrations of inhaled agonists reducing FEV1 by 20% of baseline (PC20) were 0.12 and 0.28 mg.ml-1 for bradykinin and Kallidin, respectively. When inhaled at concentrations up to 10.62 mg.ml-1, [desArg9]-bradykinin failed to provoke any significant fall in FEV1 from baseline in any of the subjects studied. Following recovery from the second bradykinin challenge, provocation with Kallidin revealed a reduced response to this agonist, the PC20 value increasing from 0.28 to 1.23 mg.ml-1. Similarly, once the airways had recovered from the second Kallidin challenge, provocation with bradykinin also showed a reduced response, the PC20Bk increasing from 0.12 to 0.94 mg.ml-1. Surprisingly, despite failing to cause bronchoconstriction, repeated exposures with inhaled [desArg9]-bradykinin reduced the airway response to bradykinin, the PC20Bk increasing from 0.12 to 0.41 mg.ml-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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Comparative nasal effects of bradykinin, Kallidin and [Des-Arg9]-bradykinin in atopic rhinitic and normal volunteers.
The Journal of physiology, 1991Co-Authors: K Rajakulasingam, Riccardo Polosa, S. T. Holgate, Peter H. HowarthAbstract:1. The structure-activity relationship of kinins within the nose has been investigated in atopic rhinitic (n = 7) and non-rhinitic (n = 7) subjects. On 4 separate days, each separated by a week, subjects randomly underwent nasal challenge with incremental doses of either the B1 agonist [Des-Arg9]-bradykinin, the B2 agonists Kallidin or bradykinin, or vehicle placebo in a double-blind comparative study. The nasal response was monitored objectively by measurement of nasal airways resistance (NAR) by active posterior rhinomanometry and subjectively by symptom reporting of nasal blockage, rhinorrhoea, nasal itch and nasal pain. 2. The B2 agonists Kallidin and bradykinin both induced a dose-dependent increase in NAR (P less than 0.001) and were associated with symptomatic reporting of nasal blockage (P less than 0.05), rhinorrhoea (P less than 0.01) and nasal discomfort (P less than 0.05) compared to placebo. In contrast the effects of the B1 agonist [Des-Arg9]-bradykinin on NAR and symptom reporting were indistinguishable from placebo. No difference could be identified in the nasal response to Kallidin and bradykinin between rhinitic and non-rhinitic subjects and there was no evidence of B1 receptor upregulation in the disease state. For the whole group the provocative dose of agonist inducing a 50% increase in NAR (PD50) was 1.77 x 10(-4) mol for bradykinin and 2.86 x 10(-4) mol for Kallidin (P greater than 0.05). 3. These findings identify that the nasal effects of kinins are mediated through B2 receptors and the advent of B2 receptor antagonists will permit a further evaluation of the role of kinins in rhinitis.
Stein Knardahl - One of the best experts on this subject based on the ideXlab platform.
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Contraction-related factors affect the concentration of a Kallidin-like peptide in rat muscle tissue.
The Journal of physiology, 2002Co-Authors: Fernando Boix, Ulrich Hilgenfeldt, Laila Rosenborg, Stein KnardahlAbstract:In order to study the effects of the manipulation of various factors related to muscular activity on the concentration of kinins in muscular tissue, a microdialysis probe was implanted in the adductor muscle of the hindlimb in anaesthetized rats. After collection of baseline samples, the perfusion fluid was changed to a Ringer solution containing sodium lactate (10 or 20 mM), adenosine (50 or 100 microM) or a lower pH (7.0 or 6.6). Whereas perfusion with lactate did not have any significant effect on the concentration of kinins in the dialysate, the perfusion with a lower pH or with adenosine dose-dependently increased the kinin content in the samples. In a second microdialysis experiment, by using specific radioimmunoassays (RIA) for bradykinin and Kallidin, we observed that about 70 % of the total kinins dialysed from rat muscle are a Kallidin-like peptide. Also, the simultaneous perfusion with 100 microM caffeine totally abolished the increase in kinin levels induced by the perfusion at pH 6.6. In a third experiment, soleus muscles from rat were stimulated in vitro during 30 min in the presence or absence of 77 microM caffeine. Electrically stimulated contraction, but not the addition of 10 mU ml(-1) insulin, induced an increase in the concentration of the Kallidin-like peptide in the buffer. This effect was totally prevented by the addition of the adenosine antagonist caffeine. These results show that a Kallidin-like peptide is released from rat muscle, and that its production is enhanced by muscle activity. Furthermore, the increase in kinin peptides during muscle contraction may be mediated by an increase in adenosine levels.
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Contraction‐related factors affect the concentration of a Kallidin‐like peptide in rat muscle tissue
The Journal of Physiology, 2002Co-Authors: Fernando Boix, Ulrich Hilgenfeldt, Laila Rosenborg, Stein KnardahlAbstract:In order to study the effects of the manipulation of various factors related to muscular activity on the concentration of kinins in muscular tissue, a microdialysis probe was implanted in the adductor muscle of the hindlimb in anaesthetized rats. After collection of baseline samples, the perfusion fluid was changed to a Ringer solution containing sodium lactate (10 or 20 mm), adenosine (50 or 100 μM) or a lower pH (7.0 or 6.6). Whereas perfusion with lactate did not have any significant effect on the concentration of kinins in the dialysate, the perfusion with a lower pH or with adenosine dose-dependently increased the kinin content in the samples. In a second microdialysis experiment, by using specific radioimmunoassays (RIA) for bradykinin and Kallidin, we observed that about 70 % of the total kinins dialysed from rat muscle are a Kallidin-like peptide. Also, the simultaneous perfusion with 100 μM caffeine totally abolished the increase in kinin levels induced by the perfusion at pH 6.6. In a third experiment, soleus muscles from rat were stimulated in vitro during 30 min in the presence or absence of 77 μM caffeine. Electrically stimulated contraction, but not the addition of 10 mU ml−1 insulin, induced an increase in the concentration of the Kallidin-like peptide in the buffer. This effect was totally prevented by the addition of the adenosine antagonist caffeine. These results show that a Kallidin-like peptide is released from rat muscle, and that its production is enhanced by muscle activity. Furthermore, the increase in kinin peptides during muscle contraction may be mediated by an increase in adenosine levels.
