In this study we evaluated the mechanisms underlying s.c. and spinal intrathecal (i.t.) nicotine inhibition of bradykinin-induced plasma extravasation in the knee joint of the rat (J. Pharmacol. Exp. Ther. 262: 889-895, 1992; ibid., 264: 839-844, 1993). The dose-response curve for the inhibitory action of s.c. nicotine on bradykinin-induced plasma extravasation was attenuated by adrenal medullectomy and by intra-articular perfusion of ICI-118,551 (a beta-2 adrenoceptor antagonist). In addition, the dose-response curve of s.c. nicotine was attenuated by acute surgical lumbar sympathectomy and by intra-articular phentolamine (an alpha adrenoceptor antagonist). The dose-response curve for i.t. nicotine (up to 1 mg/kg) was not attenuated by intra-articular ICI-118,551 and was potentiated by adrenal medullectomy. The action of i.t. nicotine was also not affected by intra-articular phentolamine or by acute surgical lumbar sympathectomy. These results suggest that the inhibition of bradykinin-induced ...
The purpose of these experiments was to study the possible contribution of bradykinin to normal blood pressure maintenance. The bradykinin analogue B4146, a competitive antagonist-partial agonist of bradykinin, was used in three groups of normotensive unanesthetized Wistar rats. Two intra-aortic injections of B4146 (1 mg in 0.2 ml of dextrose) were given 5 minutes apart (i.e., well after return of blood pressure to baseline, which occurred within 68 +/- 19 seconds). One group had been pretreated with the angiotensin converting enzyme inhibitor HOE 498, 1 mg/kg (Hoechst), and one received only dextrose as the first injection to serve as controls. The bradykinin antagonist produced an average increase in mean arterial pressure of approximately 13 mm Hg for all groups. In five animals, however, the first injection of B4146 produced a hypotensive effect, whereas the second one consistently produced a rise in blood pressure. Pretreatment with the angiotensin converting enzyme inhibitor did not affect ...
Sigma-Aldrich offers abstracts and full-text articles by [Kouki Makitani, Shota Nakagawa, Yasuhiko Izumi, Akinori Akaike, Toshiaki Kume].
Synthetic bradykinin (SBR 640) was assayed on the isolated hearts of the guinea pig, the rabbit, the cat, the dog, and the rat. With the exception of the rats heart, all reacted strongly to bradykinin with an increase in coronary flow. The guinea pigs heart was by far the most sensitive, reacting to concentrations of bradykinin of the order of 10-9 to 10-10 and therefore being as sensitive as the rats uterus and rats duodenum, so far the preparations most sensitive to bradykinin. On the dynamics of a normally beating heart, the effects of bradykinin are slight or trivial. When the amplitude or rate is reduced, bradykinin tends to increase both. There was, however, no relationship between its effects on the frequency or amplitude and its strong vasodilating effect on the coronary vessels. Since there was no tachyphylaxis to even threshold doses of bradykinin, the conclusion is drawn that it affects directly the coronary bed through its typical vasodilating action.. The possibility of ...
Bradykinin is a potent endothelium-dependent vasodilator, leading to a drop in blood pressure. It also causes contraction of non-vascular smooth muscle in the bronchus and gut, increases vascular permeability and is also involved in the mechanism of pain.[4] Bradykinin also causes natriuresis, contributing to the drop in blood pressure. Bradykinin raises internal calcium levels in neocortical astrocytes causing them to release glutamate, though this finding has only been confirmed in-vitro.[5] Bradykinin is also thought to be the cause of the dry cough in some patients on widely prescribed angiotensin-converting enzyme (ACE) inhibitor drugs. It is thought that bradykinin is converted to inactive metabolites by ACE, therefore inhibition of this enzyme leads to increased levels of bradykinin, which causes a dry cough via bronchoconstriction. In severe cases, the elevation of bradykinin may result in angioedema, a medical emergency.[6] People of African descent have up to 5x increased risk of ACE ...
To determine whether cold could activate the kallikrein-kinin system in vivo as it does in vitro, the circulating systemic concentrations of bradykinin were serially measured in 10 cyildren with congenital diseases of the heart undergoing corrective cardiac surgery. Bradykinin was measured by radioimmunoassay in blood samples obtained before, during and after profound hypothermia (to 18 degrees C) and cardiopulmonary bypass. The circulating concentrations of bradykinin increased significantly as body temperature decreased during surface cooling. The increase in circulating bradykinin was associated with a decrease in the circulating level of bradykininogen, the precursor of bradykinin. With the onset of cardiopulmonary bypass and hence, removal of the lung and pulmonary converting enzyme from the circulation, there was a further rise in the already elevated concentrations of bradykinin. This is the first in vivo demonstration that hypothermia leads to an increase in the circulating ...
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... Identifiers CAS number 58-82-2 PubChem 6026 MeSH Bradykinin Properties Molecular formula C50H73N15O11 Molar mass 1060.21 Except where
BACKGROUND The effect of small and high doses of intracerebroventricularly (icv) applied bradykinin (BK) on nociception produced by mechanical stimuli and the participation of B1 and B2 receptors in this nociception were investigated in rats. RESULTS BK at the lowest dose (0.06 μg) produced hyperalgesia whereas at the higher doses (6 and 12 μg) antinociception. This effect was abolished by B1 or B2 receptor antagonists, des-Arg(10)-HOE140 and HOE140 (1 pmol icv), respectively. CONCLUSION Depending on the dose used, BK produces pro- or anti-nociceptive action. Both B1 and B2 receptors are involved in the action of icv applied BK.
The effects of combined NEP and ACE inhibition on angiotensin and bradykinin peptide levels largely represented the summation of the effects of separate NEP and ACE inhibition. NEP inhibition alone produced diuresis, natriuresis, increased urine cyclic GMP and BK-(1-9) levels, increased Ang II and Ang I levels in plasma and increased Ang I levels in heart. NEP inhibition also decreased BK-(1-7) and BK-(1-9) levels in blood and decreased the BK-(1-7)/BK-(1-9) ratio in urine, blood and heart. ACE inhibition alone reduced Ang II levels in kidney, and increased BK-(1-9) levels in blood, kidney and aorta. ACE inhibition also decreased Ang II/Ang I ratio in plasma, kidney, heart and lung, and decreased BK-(1-7)/BK-(1-9) ratio in blood and kidney. In addition to summation of the effects of separate NEP and ACE inhibition, interaction between the two inhibitors did occur. Perindopril potentiated the effects of ecadotril on diuresis, natriuresis and urine BK-(1-7)/BK-(1-9) ratio, and combined NEP/ACE ...
To test the hypothesis that the effects of endogenously produced bradykinin on glomerular and tubular function are age dependent, physiological responses to administration of the specific B2-receptor antagonist icatibant were measured in conscious, chronically instrumented 1- and 6-wk-old lambs. Novel findings of our experiments are as follows. 1) In response to icatibant administration, there was an ∼80% decrease in GFR at 20 min in 1-wk-old lambs that was sustained for 60 min; in 6-wk-old lambs, there was an ∼70% decrease in GFR by 20 min, with control levels reached by 40 min. 2) Administration of icatibant was associated with a significant decrease in urinary flow, Cl−, and K+ excretion rates that were similar in both groups of lambs. 3) In 6- but not 1-wk-old lambs, Na+ excretion decreased 20 min after icatibant administration, returning toward control at 40 min. 4) PRA increased by 20 min after icatibant administration in both age groups; this effect was more pronounced and prolonged ...
Bradykinin produced at sites of tissue injury and inflammation elicits acute pain and alters the sensitivity of nociceptive neurons to subsequent stimuli. We tested the hypothesis that bradykinin could elicit long-lasting changes in nociceptor function by activating members of the nuclear factor of activated T-cells (NFAT) family of transcription factors. Bradykinin activation of B2 receptors evoked concentration-dependent (EC50 = 6.0 ± 0.3 nM) increases in intracellular Ca2+ concentration ([Ca2+]i) in a proportion of dorsal root ganglion neurons in primary culture. These [Ca2+] increases were sensitive to inhibition of phospholipase C (PLC) and depletion of Ca2+ stores. In neurons expressing a green fluorescent protein (GFP)-NFAT4 fusion protein, a 2-min exposure to bradykinin induced the translocation of GFP-NFAT4 from the cytoplasm to the nucleus. Translocation was partially inhibited by the removal of extracellular Ca2+ and was blocked by inhibition of calcineurin. Furthermore, bradykinin ...
Angiotensin converting enzyme (ACE) can raise blood pressure through the renin-angiotensin system, which alters kidney function. The enzyme is zinc dependent. ACE can hydrolyze and inactivate a nine amino acid blood vessel dilator, bradykinin. Loss of the blood vessel dilation from bradykinin causes some high blood pressure. ACE inhibition can successfully treat hypertension and heart […]. View Post ...
The sole role of bradykinin (BK) as an inflammatory mediator is controversial, as recent data also support an anti-inflammatory role for BK in Alzheimers disease (AD). The involvement of two different receptors (B1R and B2R) could be a key to understand this issue. However, although copper and zinc dyshomeo Zinc in the Biosciences
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The mechanisms of action whereby these medications prevent type 2 diabetes are speculative25. ACE inhibitors not only block the conversion of angiotensin I to angiotensin II, but also increase bradykinin levels through inhibition of kininase II-mediated degradation57,58. These higher levels lead to increased production of prostaglandins E^sub 1^ and E^sub 2^ and nitric oxide, which improve exercise-induced glucose metabolism59 and muscle sensitivity to insulin60-62, resulting in enhanced insulinmediated glucose uptake. Furthermore, the peripheral vasodilatory actions of ACE inhibitors and ARBs lead to an improvement in skeletal muscle blood flow, the primary target for insulin action and an important determinant of glucose uptake. This effectively increases the surface area for glucose exchange between the vascular bed and skeletal muscles. Clinical evidence supporting this effect has been provided by Morel and coworkers63, who have shown improved insulin sensitivity when enalapril was given for ...
PubMed lists over 1,500 papers with U73122 in the abstract. The large majority use the inhibitor simply as a tool to check that some signaling pathway requires PLC. However, numerous papers report additional unexpected effects, raising question whether this agent can be used as a pharmacological tool without serious side effects. We select results from just four early papers. The initial brief announcement of U73122 from Upjohn reports that it inhibits partially purified PLC in vitro when the molar ratio of Ca2+:PI in the assay was ,2, but "increased PLC activity" when the molar ratio was 4-12 (Bleasdale et al., 1989). There are no data or experimental details in that book chapter. A careful study in NG108-15 neuroblastoma-glioma cells and in dorsal root ganglion cells shows that U73122 blocks bradykinin-induced Ca2+ transients irreversibly with a steep dose-response curve and a half-effective dose IC50 of 200 nM for 20-min preincubations and that U73343 is without effect (Jin et al., 1994). ...
Figure shows the cumulative responses of bronchiolar strips to exogenously added bradykinin. The data are expressed relative to the maximal tension developed in response to a standard agonist, methacholine (a cholinergic drug). Both normal and denuded strips were tested in the presence and absence of a novel drug (BP239). The data are mean values, the error bars have been deleted for the sake of clarity. The responses of normal and denuded strips in the absence of BP239 were significantly different from each other. However in the presence of BP239 no differences were noted between normal and denuded strips.. Comments:. Several possible explanations can be given. For instance, the epithelium could be producing an inhibitory substance that either limited responses to the peptide or even degraded it, it could have acted as a mere barrier to the access of bradykinin to the receptor, etc. Again the novel drug could be a general antagonist to bradykinin or to the production of some substance released ...
Contact ePrints Soton: [email protected] ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2. This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.. ...
Make 40 mL. ~4 µL 1 mg/mL stock per 1 mL working solution. Each 21.2 µL aliquot of 1 mg/mL makes 5 mL 2µM working solution. 169.6 µL 1 mg/mL stock in 40 mL HBS (8 aliquots). Make 24 aliquots of 1.6 mL (16 for Lab 7.1, 8 for Lab 7.2). ...
Bradykinin receptor B1 (B1) is a G-protein coupled receptor encoded by the BDKRB1 gene in humans. Its principal ligand is bradykinin, a 9 amino acid peptide generated in pathophysiologic conditions such as inflammation, trauma, burns, shock, and allergy. The B1 receptor is one of two of G protein-coupled receptors that have been found which bind bradykinin and mediate responses to these pathophysiologic conditions. B1 protein is synthesized de novo following tissue injury and receptor binding leads to an increase in the cytosolic calcium ion concentration, ultimately resulting in chronic and acute inflammatory responses. Classical agonist of this receptor includes bradykinin1-8 (bradykinin with the first 8 amino acid) and antagonist includes [Leu8]-bradykinin1-8. LF22-0542 Bradykinin receptor GRCh38: Ensembl release 89: ENSG00000100739 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000041347 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". "Entrez Gene: BDKRB1 ...
Our data indicate that bradykinin production is increased during cardiac anaphylaxis, a reaction characterized by the release of several coronary-vasoconstricting mediators. The following findings define the functional consequences of this increased bradykinin production: (1) HOE 140 potentiates anaphylactic coronary vasoconstriction and exacerbates arrhythmias. (2) When the half-life of bradykinin is prolonged with captopril and enalaprilat, anaphylactic coronary vasoconstriction is greatly diminished, or even reversed, and arrhythmias are alleviated. (3) HOE 140 prevents the effects of the kininase II/ACE inhibitors. Accordingly, we postulate that bradykinin functions as a mitigating factor in cardiac anaphylaxis by opposing the coronary-vasoconstricting effects of other mediators.. Given the potent coronary-vasodilating effects of bradykinin7 and the likelihood that this peptide is a mediator of immediate hypersensitivity,13 we questioned whether local bradykinin production is augmented ...
Bradykinin as the major product of the contact-kinin system triggers inflammation and brain edema formation (for a comprehensive overview, see [2]). In this study, we aimed at targeting FXIIa, the very first step required for activation of this pathway in the plasma to alleviate pathological events leading to secondary injury after brain trauma.. Following brain trauma, bradykinin levels in the cerebrospinal fluid of patients are markedly elevated up to 48 h and decrease thereafter, reaching levels of the control group within 72 h after injury [19]. Similar to the human situation, bradykinin levels maximally increase within 2 h in the brain tissue of mice after experimentally induced focal brain trauma and then subsequently decline [7]. In accordance, we observed that plasma bradykinin levels increased twofold to threefold within 2 h after focal cortical injury in mice. As FXIIa activates plasma kallikrein, it is plausible to assume that posttraumatic bradykinin release is dependent on the ...
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 ...
The major new finding of the present study is that Hoe140, a bradykinin BK2-receptor antagonist, inhibited the captopril-induced change in CBF autoregulation. The result suggests that the modulation of CBF autoregulation by captopril is mediated, at least in part, by bradykinin.. In a previous report, in which Hoe140 (0.75 nmol) was infused into the aorta in Sprague-Dawley rats, bradykinin-induced hypotension was still impaired by 71% 1 hour after infusion.13 In the present intravenous study, the dose of Hoe140 was similar to or even greater than that in the previous study, and it completely prevented the hypotensive effect of bradykinin. In a steady state, Hoe140 concentration in the circulating blood should be constant in the whole body, including cerebral vessels. This means that a sufficient concentration of Hoe140 to block BK2 receptors should have reached cerebral arteries during the experiment. Furthermore, there is no report that the distribution of BK2 receptor is different between ...
The first total synthesis of martinellic acid, a naturally occurring bradykinin receptor antagonist, via a Cul-catalyzed coupling reaction of β-amino ester 6 with 1,4-diiodobenzene and a guanylation reaction of secondary amine 3 under mild conditions as key steps, is described ...
MediLumine has licensed a set of bradykinin receptor modulators developed by scientists at University of Sherbrooke for in vivo and in vitro research. These receptor modulators are available for preclinical research exclusively through MediLumine are based in a proprietary sequence of natural and unnatural amino acids which resist enzymatic degradation, have a superior pharmacokinetic profile and are selective for both animal human versions of the bradykinin receptors.. As a tool for research, bradykinin receptor agonism is used in various in-vivo animal models of disease which involve up-regulation of Bradykinin receptors. For example, the blood-brain barrier (BBB), a powerful physiological barrier that seriously impairs the delivery of various therapeutic compounds to the brain can be transiently opened with agonism of the Bradykinin B2 Receptor. The blood brain tumor barrier can be selectively opened with bradykinin B1R receptor agonism thus increasing delivery of imaging agents and ...
Home » Bradykinin. Bradykinin (Science: protein) vasoactive nonapeptide (RPPGFSPFR) formed by action of proteases on kininogens. Very similar to kallidin (which has the same sequence but with an additional N terminal lysine). Bradykinin is a very potent vasodilator and increases permeability of post capillary venules, it acts on endothelial cells to activate phospholipase A2. It is also spasmogenic for some smooth muscle and will cause pain. ...
OBJECTIVE To investigate whether generation and liberation of bradykinin and histamine contribute to generalized edema formation in pediatric cardiopulmonary bypass surgery. DESIGN Prospective observational study. SETTING Pediatric heart surgery of a university hospital. PATIENTS Forty-one neonates, infants, and children undergoing cardiopulmonary bypass to correct congenital cardiac anomalies. INTERVENTIONS Plasma concentrations of bradykinin and histamine were determined before, during, and after cardiopulmonary bypass. Fluid balance was evaluated by control of fluid intake and output. MEASUREMENTS AND MAIN RESULTS The susceptibility to generalized edema formation increased significantly (r = -.457; p |.005) with decreasing age. Approximately three times higher plasma concentrations of bradykinin (p |.001) were found at the onset of anesthesia and during the total observation period in patients with a fluid retention of |6% of body weight compared with patients with a lower retention rate.
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TY - JOUR. T1 - Preclinical pharmacology, ocular tolerability and ocular hypotensive efficacy of a novel non-peptide bradykinin mimetic small molecule. AU - Sharif, Najam A.. AU - Li, Linya. AU - Katoli, Parvaneh. AU - Xu, Shouxi. AU - Veltman, James. AU - Li, Byron. AU - Scott, Daniel. AU - Wax, Martin. AU - Gallar, Juana. AU - Acosta, Carmen. AU - Belmonte, Carlos. PY - 2014/11/1. Y1 - 2014/11/1. N2 - We sought to characterize the ocular pharmacology, tolerability and intraocular pressure (IOP)-lowering efficacy of FR-190997, a non-peptidic bradykinin (BK) B2-receptor agonist. FR-190997 possessed a relatively high receptor binding affinity (Ki=27nM) and a high invitro potency (EC50=18.3±4.4nM) for inositol-1-phosphate generation via human cloned B2-receptors expressed in host cells with mimimal activity at B1-receptors. It also mobilized intracellular Ca2+ in isolated human trabecular meshwork (h-TM), ciliary muscle (h-CM), and in immortalized non-pigmented ciliary epithelial (h-iNPE) cells ...
TY - JOUR. T1 - Enhanced responsiveness of cardiac vagal chemosensitive endings to bradykinin in heart failure. AU - Schultz, Harold D. AU - Wang, Wei. AU - Ustinova, Elena E.. AU - Zucker, Irving H. PY - 1997/10/18. Y1 - 1997/10/18. N2 - There is good evidence that the cardiopulmonary and arterial baroreflexes are blunted in chronic heart failure (HF). Other evidence, however, suggests that the cardiac chemoreflex is enhanced during HF. In the present study, we sought to determine whether HF alters the sensitivity of cardiac vagal chemosensitive endings to bradykinin (BK), an endogenous mediator that activates ventricular C fiber afferents. We measured the activity of cardiac vagal single fibers and compared the afferent responses to left atrial injections of BK and capsaicin in sham-operated and pacing- induced HF dogs. The capsaicin-sensitive endings did not respond to changes in cardiac pressures evoked by vascular snares and were C fiber endings (0.8- 2.1 m/s). Most were located in the left ...
We used combined patch-clamp-microfluorimetric recordings to examine the effects of bradykinin on [Ca2+]i transients and the Ca2+ current (ICa) in rat dorsal root ganglion neurons in vitro. Bradykinin increased [Ca2+]i in approximately 20% of dorsal root ganglion cells examined and inhibited the ICa in approximately 65% of dorsal root ganglion cells. Bradykinin also inhibited the ICa when [Ca2+]i was buffered with 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid or when Ba2+ was the charge carrier. When ICas of increasing duration were elicited in these neurons, [Ca2+]i transients were produced that increased in amplitude but eventually approached an asymptote at longer voltage steps. Similarly, the amplitude of the [Ca2+]i transient also approached an asymptote in current-clamp recordings when cells were induced to fire a large number of action potentials. The bradykinin-induced inhibition of the amplitude of the [Ca2+]i transient was more pronounced at shorter voltage steps. At pulse ...
Sigma-Aldrich offers Sigma-B6769, des-Arg9-[Leu8]-Bradykinin acetate salt for your research needs. Find product specific information including CAS, MSDS, protocols and references.
Abstract: Components of the blood kinin system as well as concentration of kininogen and kininase activity were studied in various myocardial structures after controlled restriction of coronary circulation by 30%, 50%, 70% and 90% within 30 min. As blood supply of heart decreased, activation of kallikrein, decrease in content of kininogen and inhibition of kininase activity in blood were observed. These alterations were detected also in myocardium; they were especially distinct in the ischemic zone ...
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a, BK-induced calcium wave in an N1E-115 neuroblastoma. At time = 0, 500 nM BK was externally applied to the bathing medium of a cell stained with fura-2. Fluor
Affiliation:東海大学,開発工学部,教授, Research Field:Biomedical engineering/Biological material science, Keywords:カルシウムイオン,PATCH-CLAMP METHOD,ラミニン,培養神経細胞,疼痛除去,BRADYKININ,脊髄後根神経節,パッチクランプ法,活動電位,低出力レーザー, # of Research Projects:1, # of Research Products:0
TY - JOUR. T1 - Endothelium-derived hyperpolarizing factor mediates bradykinin-stimulated tissue plasminogen activator release in humans. AU - Rahman, Ayaz M.. AU - Murrow, Jonathan R.. AU - Ozkor, Muhiddin A.. AU - Kavtaradze, Nino. AU - Lin, Ji. AU - De Staercke, Christine. AU - Hooper, W. Craig. AU - Manatunga, Amita. AU - Hayek, Salim. AU - Quyyumi, Arshed A.. PY - 2014/1/1. Y1 - 2014/1/1. N2 - Bradykinin (BK) stimulates tissue plasminogen activator (t-PA) release from human endothelium. Although BK stimulates both nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) release, the role of EDHF in t-PA release remains unexplored. This study sought to determine the mechanisms of BK-stimulated t-PA release in the forearm vasculature of healthy human subjects. Methods: In 33 healthy subjects (age 40.3 ± 1.9 years), forearm blood flow (FBF) and t-PA release were measured at rest and after intra-arterial infusions of BK (400 ng/min) and sodium nitroprusside (3.2 mg/min). Measurements ...
People who take ACE inhibitors may develop angioedema, a condition that causes itchy and painful swelling beneath the skin around the eyes, lips, tongue, throat, hands, or feet. In severe cases, the throat may swell, obstructing the airway and leading to breathing difficulty. ACE inhibitors prevent the breakdown of a natural chemical in the body called bradykinin. Increased levels of bradykinin, which can cause swelling, may contribute to the development of angioedema. Blocking bradykinin receptor cells prevents bradykinin from initiating swelling and may lead to a possible decrease in angioedema symptoms. The purpose of this study is to evaluate the effectiveness of HOE-140, a bradykinin receptor blocker, at reducing symptoms in people with ACE inhibitor-associated angioedema.. This study will enroll people admitted to the emergency room or hospital who have a severe case of ACE inhibitor-associated angioedema. Participants will be randomly assigned to receive an injection of either HOE-140 or ...
The gene encoding a putative mouse bradykinin B1 receptor was cloned from a genomic library by low stringency screening. Analysis of two isolated clones revealed a region which contains an open reading frame uninterrupted by introns and encodes a 334 amino acid protein, which exhibits seven potential transmembrane domains and is 68% identical to the human and rabbit bradykinin B1 receptors, Lipopolysaccharide-treatment induces B1 receptor transcripts in the heart, liver and lung, Stable expression of the coding region in COS-7 cells resulted in high levels of binding sites for the specific B1 ligand des-Arg(10) kallidin (K-d = 1.3 nM; B-max = 51 fmol/mg protein). the rank order of affinity of the receptor for the agonists and antagonists was: des Arg(9)BKdes-Arg(9)Leu(8)BKdrs-Arg(10)kallidin much greater than Hoe-140 = bradykinin. Functional coupling of the cloned receptor was demonstrated by the dose-dependent effect of des-Arg(9)BK on the extracellular acidification rate in stably transfected ...
The kinin B1-receptor which is absent or expressed at very low levels under physiological conditions is strongly induced under inflammatory conditions. It has been shown that B1-receptor induction during inflammation involves interleukin-1 beta (IL-1 beta) production and activation of nuclear factor-kappa B (NF-kappa B). Since bradykinin (BK), the B2-receptor agonist induces IL-1 beta expression and activates NF-kappa B, we have analysed the effect of B2-receptor activation in cultured human lung fibroblasts cells on B1-receptor expression by a semiquantitative RT-PCR analysis. Treatment with BK resulted in a significant increase in the expression of B1-receptor mRNA which was abolished by a specific B2-receptor antagonist. This result suggests that B2-receptor activation can prime the expression of B1-receptors. Although the renal localisation of the B2-receptor has been thoroughly studied, nothing is known about the distribution of the B1-receptor in the kidney. Using a combination of ...
TY - JOUR. T1 - Prostaglandin E2 enhances bradykinin-stimulated release of neuropeptides from rat sensory neurons in culture. AU - Vasko, M. R.. AU - Campbell, W. B.. AU - Waite, K. J.. PY - 1994/8/1. Y1 - 1994/8/1. N2 - Prostaglandins are known to enhance the inflammatory and nociceptive actions of other chemical mediators of inflammation such as bradykinin. One possible mechanism for this sensitizing action is that prostanoids augment the release of neuroactive substances from sensory neurons. To initially test this hypothesis, we examined whether selected prostaglandins could enhance the resting or bradykinin-evoked release of immunoreactive substance P (iSP) and/or immunoreactive calcitonin gene-related peptide (iCGRP) from sensory neurons in culture. Bradykinin alone causes a concentration-dependent increase in the release of iSP and iCGRP from isolated sensory neurons, and this action is abolished in the absence of extracellular calcium. Pretreating the neurons with PGE2 (10 nM to 1 μM) ...
TY - JOUR. T1 - Role of heat shock protein 90 in bradykinin-stimulated endothelial nitric oxide release. AU - Harris, M. Brennan. AU - Ju, Hong. AU - Venema, Virginia J.. AU - Blackstone, Michele. AU - Venema, Richard C.. PY - 2000/12/1. Y1 - 2000/12/1. N2 - Previously we described ENAP-1, a 90-kDa protein that is tyrosine-phosphorylated in endothelial cells in response to bradykinin (BK) stimulation and is associated with endothelial nitric oxide synthase (eNOS). Subsequently, other investigators demonstrated that eNOS interacts with heat shock protein 90 (Hsp90) following stimulation of endothelial cells with vascular endothelial growth factor (VEGF), histamine, or fluid shear stress. Therefore, we tested the hypotheses that ENAP-1 and Hsp90 are the same protein and that BK activation of eNOS is dependent on Hsp90. Immunoblotting of immunoprecipitated Hsp90 with anti-phosphotyrosine antibody shows that Hsp90 is tyrosine-phosphorylated in response to BK stimulation of bovine aortic endothelial ...
Abstract: : Purpose:Bradykinin (BK) stimulates B2 kinin receptors to activate multiple signaling pathways in trabecular meshwork (TM) cells. The objective of the present study was to investigate effects of BK signaling on secretion of matrix metalloproteinases (MMP) by TM cells and the consequences of these effects on outflow facility. Methods: Experiments on BK signaling and MMP secretion were performed in primary cultures of TM cells studied at passages 2 and 3. Determinations of outflow facility were conducted in preparations of isolated anterior segments perfused at constant pressure of 10 mmHg. Results:Incubation of bovine or human TM cells with BK produced a concentration-dependent increase in intracellular free Ca2+. The dose-response relationship was similar for bovine and human cells, with the response maximum occurring at 100 nM BK and an EC50 of 3 nM. This effect was blocked by pretreatment of cells with Hoe-140, a B2 receptor antagonist. Bk treatment also produced a 10-fold increase ...
In the absence of C1-esterase inhibitor protein activity (the yellow dots) bradykinin production continues uncontrolled. FXII is factor XII a component of the blood clotting cascade. Bradykinin increases blood vessel diameter and pore size with leaking resulting in swelling of the tissue through which the blood vessels travel. It is so powerful that 1 microgram injected into the brachial artery increases arm blood flow 6 fold. Dental treatment, particularly tooth extraction, is a recognized trigger of HAE though symptoms may not manifest for many hours or even days after the procedure. A typical course resolves in 5 to 7 days, but in some patients, the clinical manifestations exist up to 6 weeks. Other known triggers are physical/psychological stress, fatigue, menstrual periods, pregnancy, trauma and having a breathing tube placed for anesthesia. 75% of patients with HAE have a relative who suffers from repetitive bouts of swelling. The remaining 25% are spontaneous without an affected relative. ...
AIM: To investigate the system for bradykinin (BK) to stimulate intestinal secretomotor neurons and intestinal chloride secretion. of BK or B2 receptor (B2R) agonist considerably improved the baseline set alongside the control. B2R antagonist tetrodotoxin and scopolamine (blockade of muscarinic receptors) considerably suppressed the upsurge in evoked by BK. The BK-evoked was suppressed by cyclooxygenase (COX)-1 or COX-2 particular inhibitor aswell as non-selective COX inhibitors. Preincubation of submucosa/mucosa arrangements with BK for 10 min considerably increased PGE2 creation which was abolished from the COX-1 and COX-2 inhibitors. The BK-evoked was suppressed by non-selective EP receptors and EP4 receptor antagonists but selective EP1 receptor antagonist didnt have a substantial influence on the BK-evoked modification. Inhibitors from the sign transductors had been pre-incubated using the cells for 10 min before evoking with BK as well as the modification was documented. The modification ...
BACKGROUND: This study investigates bradykinin and nitric oxide as potential mediators of AT2-receptor-stimulated duodenal mucosal alkaline secretion. Duodenal mucosal alkaline secretion was measured in methohexital- and alpha-chloralose-anaesthetised rats by means of in situ pH-stat titration. Immunohistochemistry and Western blot were used to identify the BK2 receptors. RESULTS: The AT2 receptor agonist CGP42112A (0.1 microg kg(-1) min(-1)) administered intravenously increased the duodenal mucosal alkaline secretion by approximately 50 %. This increase was sensitive to the selective BK2 receptor blocker HOE140 (100 ng/kg i.v.), but not to luminal administration of the NOS blocker L-NAME (0.3 mM). Mean arterial pressure did not differ between groups during the procedures. Immunohistochemistry showed a distinct staining of the crypt epithelium and a moderate staining of basal cytoplasm in villus enterocytes. CONCLUSION: The results suggest that the AT2-receptor-stimulated alkaline secretion is ...