Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Receptors, Bradykinin: Cell surface receptors that bind BRADYKININ and related KININS with high affinity and trigger intracellular changes which influence the behavior of cells. The identified receptor types (B-1 and B-2, or BK-1 and BK-2) recognize endogenous KALLIDIN; t-kinins; and certain bradykinin fragments as well as bradykinin itself.Receptor, Bradykinin B2: A constitutively expressed subtype of bradykinin receptor that may play a role in the acute phase of the inflammatory and pain response. It has high specificity for intact forms of BRADYKININ and KALLIDIN. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.Receptor, Bradykinin B1: A subtype of BRADYKININ RECEPTOR that is induced in response to INFLAMMATION. It may play a role in chronic inflammation and has a high specificity for KININS lacking the C-terminal ARGININE such as des-Arg(10)-kallidin and des-Arg(9)-bradykinin. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.Kallidin: A decapeptide bradykinin homolog cleaved from kininogen by kallikreins. It is a smooth-muscle stimulant and hypotensive agent that acts by vasodilatation.Kinins: A generic term used to describe a group of polypeptides with related chemical structures and pharmacological properties that are widely distributed in nature. These peptides are AUTACOIDS that act locally to produce pain, vasodilatation, increased vascular permeability, and the synthesis of prostaglandins. Thus, they comprise a subset of the large number of mediators that contribute to the inflammatory response. (From Goodman and Gilman's The Pharmacologic Basis of Therapeutics, 8th ed, p588)Kallikrein-Kinin System: A system of metabolic interactions by products produced in the distal nephron of the KIDNEY. These products include KALLIKREIN; KININS; KININASE I; KININASE II; and ENKEPHALINASE. This system participates in the control of renal functions. It interacts with the RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM to regulate BLOOD PRESSURE, generation of PROSTAGLANDINS, release of VASOPRESSINS, and WATER-ELECTROLYTE BALANCE.Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.Kininogens: Endogenous peptides present in most body fluids. Certain enzymes convert them to active KININS which are involved in inflammation, blood clotting, complement reactions, etc. Kininogens belong to the cystatin superfamily. They are cysteine proteinase inhibitors. HIGH-MOLECULAR-WEIGHT KININOGEN; (HMWK); is split by plasma kallikrein to produce BRADYKININ. LOW-MOLECULAR-WEIGHT KININOGEN; (LMWK); is split by tissue kallikrein to produce KALLIDIN.Receptors, Neurotransmitter: Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.Lysine Carboxypeptidase: A metallocarboxypeptidase that removes C-terminal basic amino acid from peptides and proteins, with preference shown for lysine over arginine. It is a plasma zinc enzyme that inactivates bradykinin and anaphylatoxins.Kallikreins: Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increase vascular permeability and affect smooth muscle. They act as infertility agents in men. Three forms are recognized, PLASMA KALLIKREIN (EC 3.4.21.34), TISSUE KALLIKREIN (EC 3.4.21.35), and PROSTATE-SPECIFIC ANTIGEN (EC 3.4.21.77).Captopril: A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Peptidyl-Dipeptidase A: A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, -Xaa-*-Xbb-Xcc, when neither Xaa nor Xbb is Pro. It is a Cl(-)-dependent, zinc glycoprotein that is generally membrane-bound and active at neutral pH. It may also have endopeptidase activity on some substrates. (From Enzyme Nomenclature, 1992) EC 3.4.15.1.Enalaprilat: The active metabolite of ENALAPRIL and a potent intravenously administered angiotensin-converting enzyme inhibitor. It is an effective agent for the treatment of essential hypertension and has beneficial hemodynamic effects in heart failure. The drug produces renal vasodilation with an increase in sodium excretion.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Histamine: An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Capillary Permeability: The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.Angiotensin I: A decapeptide that is cleaved from precursor angiotensinogen by RENIN. Angiotensin I has limited biological activity. It is converted to angiotensin II, a potent vasoconstrictor, after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME.Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.Thiorphan: A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms.NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Nitroprusside: A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.Coronary Vessels: The veins and arteries of the HEART.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Nitroarginine: An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6)Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Angiotensin II: An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.Biological Factors: Endogenously-synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Kininogen, High-Molecular-Weight: A plasma protein, molecular weight of 110 kD, that normally exists in plasma in a 1:1 complex with PREKALLIKREIN. HMWK is split by plasma kallikrein to produce BRADYKININ. The complex is a cofactor in the activation of coagulation factor XII. The product of this reaction, XIIa, in turn activates prekallikrein to KALLIKREINS. (From Stedman, 26th ed)Epoprostenol: A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Edema: Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Capsaicin: An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.Dinoprostone: The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.Prostaglandins E: (11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.Inositol Phosphates: Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Tetrahydroisoquinolines: A group of ISOQUINOLINES in which the nitrogen containing ring is protonated. They derive from the non-enzymatic Pictet-Spengler condensation of CATECHOLAMINES with ALDEHYDES.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Injections, Intra-Arterial: Delivery of drugs into an artery.Neprilysin: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Tachyphylaxis: Rapidly decreasing response to a drug or physiologically active agent after administration of a few doses. In immunology, it is the rapid immunization against the effect of toxic doses of an extract or serum by previous injection of small doses. (Dorland, 28th ed)Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Arginine: An essential amino acid that is physiologically active in the L-form.Tissue Kallikreins: A family of trypsin-like SERINE ENDOPEPTIDASES that are expressed in a variety of cell types including human prostate epithelial cells. They are formed from tissue prokallikrein by action with TRYPSIN. They are highly similar to PROSTATE-SPECIFIC ANTIGEN.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).

Expression of both P1 and P2 purine receptor genes by human articular chondrocytes and profile of ligand-mediated prostaglandin E2 release. (1/3087)

OBJECTIVE: To assess the expression and function of purine receptors in articular chondrocytes. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to screen human chondrocyte RNA for expression of P1 and P2 purine receptor subtypes. Purine-stimulated prostaglandin E2 (PGE2) release from chondrocytes, untreated or treated with recombinant human interleukin-1alpha (rHuIL-1alpha), was assessed by radioimmunoassay. RESULTS: RT-PCR demonstrated that human articular chondrocytes transcribe messenger RNA for the P1 receptor subtypes A2a and A2b and the P2 receptor subtype P2Y2, but not for the P1 receptor subtypes A1 and A3. The P1 receptor agonists adenosine and 5'-N-ethylcarboxamidoadenosine did not change PGE2 release from chondrocytes. The P2Y2 agonists ATP and UTP stimulated a small release of PGE2 that was potentiated after pretreatment with rHuIL-1alpha. PGE2 release in response to ATP and UTP cotreatment was not additive, but release in response to coaddition of ATP and bradykinin (BK) or UTP and BK was additive, consistent with ATP and UTP competition for the same receptor site. The potentiation of PGE2 release in response to ATP and UTP after rHuIL-1alpha pretreatment was mimicked by phorbol myristate acetate. CONCLUSION: Human chondrocytes express both P1 and P2 purine receptor subtypes. The function of the P1 receptor subtype is not yet known, but stimulation of the P2Y2 receptor increases IL-1-mediated PGE2 release.  (+info)

Endothelial function in Marfan syndrome: selective impairment of flow-mediated vasodilation. (2/3087)

BACKGROUND: The cardiovascular complications of Marfan syndrome arise due to alterations in the structural and functional properties of fibrillin, a constituent of vascular connective tissues. Fibrillin-containing microfibrils are closely associated with arterial endothelial cells, indicating a possible functional role for fibrillin in the endothelium. Plasma concentrations of endothelial cell products are elevated in Marfan subjects, which indirectly indicates endothelial dysfunction. This study directly assessed flow- and agonist-mediated endothelium-dependent brachial artery reactivity in Marfan subjects. METHODS AND RESULTS: In 20 Marfan and 20 control subjects, brachial artery diameter, blood flow, and blood pressure were measured by ultrasonic wall tracking, Doppler ultrasound, and photoplethysmography, respectively. Measurements were taken during hand hyperemia (a stimulus for endothelium-derived nitric oxide [NO] release in the upstream brachial artery) and after sublingual administration of the endothelium-independent vasodilator nitroglycerin. In 9 Marfan and 6 control subjects, the above parameters were also assessed during intra-arterial infusions of acetylcholine and bradykinin (agonists that stimulate NO production) and NG-monomethyl-L-arginine (L-NMMA, an inhibitor of NO production). Flow-mediated responses differed markedly between Marfan and control subjects (-1.6+/-3.5% versus 6. 50+/-4.1%, respectively; P<0.0001), whereas nitroglycerin produced similar vasodilation (14.2+/-5.7% versus 15.2+/-7.8%; P=NS). Agonist-induced vasodilation to incremental intra-arterial infusions of acetylcholine and bradykinin were not significantly different between Marfan and control subjects, and intra-arterial L-NMMA produced similar reductions in brachial artery diameter in both groups. CONCLUSIONS: These data demonstrate impaired flow-mediated but preserved agonist-mediated endothelium-dependent vasodilation in Marfan subjects and suggest preservation of basal NO release. Selective loss of flow-mediated dilation suggests a role for fibrillin in endothelial cell mechanotransduction.  (+info)

Bradykinin promotes ischemic norepinephrine release in guinea pig and human hearts. (3/3087)

We previously reported that bradykinin (BK; 1-1000 nM) facilitates norepinephrine (NE) release from cardiac sympathetic nerves. Because BK production increases in myocardial ischemia, endogenous BK could foster NE release and associated arrhythmias. We tested this hypothesis in guinea pig and human myocardial ischemia models. BK administration (100 nM) markedly enhanced exocytotic and carrier-mediated NE overflow from guinea pig hearts subjected to 10- and 20-min ischemia/reperfusion, respectively. Ventricular fibrillation invariably occurred after 20-min global ischemia; BK prolonged its duration 3-fold. The BK B2 receptor antagonist HOE140 (30 nM) blocked the effects of BK, whereas the B1 receptor antagonist des-Arg9-Leu8-BK (1 microM; i.e., 2.5 x pA2) did not. When serine proteinase inhibitors (500 KIU/ml aprotinin and 100 microg/ml soybean trypsin inhibitor) were used to prevent the formation of endogenous BK, NE overflow and reperfusion arrhythmias were diminished. In contrast, when kininase I and II inhibitors (DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid and enalaprilat, each 1 microM) were used to prevent the degradation of endogenous BK, NE overflow and reperfusion arrhythmias were enhanced. B2 receptor blockade abolished these effects but was ineffective if kininases were not inhibited. B2 receptor stimulation, by either exogenous or endogenous BK, also markedly enhanced carrier-mediated NE release in the human myocardial ischemia model; conversely, inhibition of BK biosynthesis diminished ischemic NE release. Because atherosclerotic heart disease impairs endothelial BK production, in myocardial ischemia BK could accumulate at sympathetic nerve endings, thus augmenting exocytotic and carrier-mediated NE release and favoring coronary vasoconstriction and arrhythmias.  (+info)

Mechanisms of prostaglandin E2 release by intact cells expressing cyclooxygenase-2: evidence for a 'two-component' model. (4/3087)

Prostaglandin (PG) release in cells expressing constitutive cyclooxygenase-1 is known to be regulated by liberation of arachidonic acid by phospholipase A2 followed by metabolism by cyclooxygenase. However, the relative contribution of phospholipase A2 to the release of PGs in cells expressing cyclooxygenase-2 is not clear. We addressed this question by using radioimmunoassay to measure PGE2 release by human cells (A549) induced to express cyclooxygenase-2 (measured by Western blot analysis) by interleukin-1beta. Cells were either unstimulated or stimulated with agents known to activate phospholipase A2 (bradykinin, Des-Arg10-kallidin, or the calcium ionophore A23187) or treated with exogenous arachidonic acid. When cells were treated to express cyclooxygenase-2, the levels of PGE2 released over 15 min were undetectable; however, in the same cells stimulated with bradykinin, A23187, or arachidonic acid, large amounts of prostanoid were produced. Using selective inhibitors/antagonists, we found that the effects of bradykinin were mediated by B2 receptor activation and that prostanoid release was due to cyclooxygenase-2, and not cyclooxygenase-1, activity. In addition, we show that the release of PGE2 stimulated by either bradykinin, A23187, or arachidonic acid was inhibited by the phospholipase A2 inhibitor arachidonate trifluoromethyl ketone. Hence, we have demonstrated that PGE2 is released by two components: induction of cyclooxygenase-2 and supply of substrate, probably via activation of phospholipase A2. This is illustrated in A549 cells by a clear synergy between the cytokine interleukin-1beta and the kinin bradykinin.  (+info)

Blocking angiotensin II ameliorates proteinuria and glomerular lesions in progressive mesangioproliferative glomerulonephritis. (5/3087)

BACKGROUND: The renin-angiotensin system is thought to be involved in the progression of glomerulonephritis (GN) into end-stage renal failure (ESRF) because of the observed renoprotective effects of angiotensin-converting enzyme inhibitors (ACEIs). However, ACEIs have pharmacological effects other than ACE inhibition that may help lower blood pressure and preserve glomerular structure. We previously reported a new animal model of progressive glomerulosclerosis induced by a single intravenous injection of an anti-Thy-1 monoclonal antibody, MoAb 1-22-3, in uninephrectomized rats. Using this new model of progressive GN, we examined the hypothesis that ACEIs prevent the progression to ESRF by modulating the effects of angiotensin II (Ang II) on the production of transforming growth factor-beta (TGF-beta) and extracellular matrix components. METHODS: We studied the effect of an ACEI (cilazapril) and an Ang II type 1 receptor antagonist (candesartan) on the clinical features and morphological lesions in the rat model previously reported. After 10 weeks of treatment with equihypotensive doses of cilazapril, cilazapril plus Hoe 140 (a bradykinin receptor B2 antagonist), candesartan, and hydralazine, we examined systolic blood pressure, urinary protein excretion, creatinine clearance, the glomerulosclerosis index, and the tubulointerstitial lesion index. We performed a semiquantitative evaluation of glomerular immunostaining for TGF-beta and collagen types I and III by immunofluorescence study and of these cortical mRNA levels by Northern blot analysis. RESULTS: Untreated rats developed massive proteinuria, renal dysfunction, and severe glomerular and tubulointerstitial injury, whereas uninephrectomized control rats did not. There was a significant increase in the levels of glomerular protein and cortical mRNA for TGF-beta and collagen types I and III in untreated rats. Cilazapril and candesartan prevented massive proteinuria, increased creatinine clearance, and ameliorated glomerular and tubulointerstitial injury. These drugs also reduced levels of glomerular protein and cortical mRNA for TGF-beta and collagen types I and III. Hoe 140 failed to blunt the renoprotective effect of cilazapril. Hydralazine did not exhibit a renoprotective effect. CONCLUSION: These results indicate that ACEIs prevent the progression to ESRF by modulating the effects of Ang II via Ang II type 1 receptor on the production of TGF-beta and collagen types I and III, as well as on intrarenal hemodynamics, but not by either increasing bradykinin activity or reducing blood pressure in this rat model of mesangial proliferative GN.  (+info)

Activation of the kallikrein-kinin system in hemodialysis: role of membrane electronegativity, blood dilution, and pH. (6/3087)

BACKGROUND: The kallikrein-kinin system activation by contact with a negatively charged surface has been promulgated to be responsible for hypersensitivity reactions. However, to explain the low frequency and heterogeneity of hypersensitivity reactions, we hypothesized that not only the electronegativity of the membrane, but also other physicochemical parameters could influence the activation of the contact phase system of plasma assessed by the measurement of kallikrein activity and bradykinin concentration. METHODS: Plasma kallikrein activity using chromogenic substrate (S2302) and plasma bradykinin concentration (enzyme immuno assay) were measured during the perfusion of human plasma (2.5 ml/min) through minidialyzers mounted with six different membranes [polyacrylonitrile (PAN) from Asahi (PANDX) and from Hospal (AN69), polymethylmethacrylate (PMMA) from Toray, cellulose triacetate (CT) from Baxter, cuprophane (CUP) from Akzo and polysulfone (PS) from Fresenius]. RESULTS: A direct relationship was shown between the electronegativity of the membrane assessed by its zeta potential and the activation of plasma during the first five minutes of plasma circulation. With the AN69 membrane, the detection of a kallikrein activity in diluted plasma but not in undiluted samples confirmed the importance of a protease-antiprotease imbalance leading to bradykinin release during the first five minutes of dialysis. With PAN membranes, the use of citrated versus heparinized plasma and the use of various rinsing solutions clearly show a dramatic effect of pH on the kallikrein activity and the bradykinin concentration measured in plasma. Finally, increasing the zeta potential of the membrane leads to a significant increase of plasma kallikrein activity and bradykinin concentration. CONCLUSIONS: Our in vitro experimental approach evidences the importance of the control of these physicochemical factors to decrease the activation of the contact system.  (+info)

Cytokine-mediated inflammatory hyperalgesia limited by interleukin-4. (7/3087)

1. The effect of IL-4 on responses to intraplantar (i.pl.) carrageenin, bradykinin, TNFalpha, IL-1beta, IL-8 and PGE2 was investigated in a model of mechanical hyperalgesia in rats. Also, the cellular source of the IL-4 was investigated. 2. IL-4, 30 min before the stimulus, inhibited responses to carrageenin, bradykinin, and TNFalpha, but not responses to IL-1beta, IL-8 and PGE2. 3. IL-4, 2 h before the injection of IL-1beta, did not affect the response to IL-1beta, whereas IL-4, 12 or 12+2 h before the IL-1beta, inhibited the hyperalgesia (-30%, -74%, respectively). 4. In murine peritoneal macrophages, murine IL-4 for 2 h before stimulation with LPS, inhibited (-40%) the production of IL-1beta but not PGE2. Murine IL-4 (for 16 h before stimulation with LPS) inhibited LPS-stimulated PGE2 but not IL-1beta. 5. Anti-murine IL-4 antibodies potentiated responses to carrageenin, bradykinin and TNFalpha, but not IL-1beta and IL-8, as well as responses to bradykinin in athymic rats but not in rats depleted of mast cells with compound 40/80. 6. These data suggest that IL-4 released by mast cells limits inflammatory hyperalgesia. During the early phase of the inflammatory response the mode of action of the IL-4 appears to be inhibition of the production TNFalpha, IL-1beta and IL-8. In the later phase of the response, in addition to inhibiting the production of pro-inflammatory cytokines, IL-4 also may inhibit the release of PGs.  (+info)

Nitric oxide limits the eicosanoid-dependent bronchoconstriction and hypotension induced by endothelin-1 in the guinea-pig. (8/3087)

1. This study attempts to investigate if endogenous nitric oxide (NO) can modulate the eicosanoid-releasing properties of intravenously administered endothelin-1 (ET-1) in the pulmonary and circulatory systems in the guinea-pig. 2. The nitric oxide synthase blocker N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 microM; 30 min infusion) potentiated, in an L-arginine sensitive fashion, the release of thromboxane A2 (TxA2) stimulated by ET-1, the selective ET(B) receptor agonist IRL 1620 (Suc-[Glu9,Ala11,15]-ET-1(8-21)) or bradykinin (BK) (5, 50 and 50 nM, respectively, 3 min infusion) in guinea-pig isolated and perfused lungs. 3. In anaesthetized and ventilated guinea-pigs intravenous injection of ET-1 (0.1-1.0 nmol kg(-1)), IRL 1620 (0.2-1.6 nmol kg(-1)), BK (1.0-10.0 nmol kg(-1)) or U 46619 (0.2-5.7 nmol kg(-1)) each induced dose-dependent increases in pulmonary insufflation pressure (PIP). Pretreatment with L-NAME (5 mg kg(-1)) did not change basal PIP, but increased, in L-arginine sensitive manner, the magnitude of the PIP increases (in both amplitude and duration) triggered by each of the peptides (at 0.25, 0.4 and 1.0 nmol kg(-1), respectively), without modifying bronchoconstriction caused by U 46619 (0.57 nmol kg(-1)). 4. The increases in PIP induced by ET-1, IRL 1620 (0.25 and 0.4 nmol kg(-1), respectively) or U 46619 (0.57 nmol kg(-1)) were accompanied by rapid and transient increases of mean arterial blood pressure (MAP). Pretreatment with L-NAME (5 mg kg(-1); i.v. raised basal MAP persistently and, under this condition, subsequent administration of ET-1 or IRL 1620, but not of U-46619, induced hypotensive responses which were prevented by pretreatment with the cyclo-oxygenase inhibitor indomethacin. 5. Thus, endogenous NO appears to modulate ET-1-induced bronchoconstriction and pressor effects in the guinea-pig by limiting the peptide's ability to induce, possibly via ET(B) receptors, the release of TxA2 in the lungs and of vasodilatory prostanoids in the systemic circulation. Furthermore, it would seem that these eicosanoid-dependent actions of ET-1 in the pulmonary system and on systemic arterial resistance in this species are physiologically dissociated.  (+info)

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 ...
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 ...
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
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 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 - 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 ...
Sérgio Henrique Ferreira (October 4, 1934 - July 17, 2016) was a Brazilian physician and pharmacologist noted for the discovery of the bradykinin potentiating factor, which led to new and widely used anti-hypertension drugs - the ACE inhibitors. Ferreira received his M.D. from the Faculty of Medicine of Ribeirão Preto of the University of São Paulo (USP) and soon became staff member of the same school, where he is a member of the Department of Pharmacology. His research training in pharmacology initiated in this Department with Prof. Maurício Rocha e Silva, the discoverer of bradykinin. While working on this subject, he discovered a family of peptides present in the venom of a Brazilian snake, Bothrops jararaca, which inhibited kininase activity and strongly potentiated the effects of bradykinin in vivo and in vitro. This factor was named bradykinin potentiating factor, BPF. In 1968, with the collaboration of Dr. Lewis Joel Greene, from the Brookhaven National Laboratory, U.S., he isolated ...
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 ...
Wang, T.; Axelsson, M.; Jensen, J.; Conlon, J.M., 2000: Cardiovascular actions of python bradykinin and substance P in the anesthetized python, Python regius
GTPases of the Rho family regulate actinomyosin-based contraction in non-muscle cells. Activation of Rho increases contractility, leading to cell rounding and neurite retraction in neuronal cell lines. Activation of Rac promotes cell spreading and interferes with Rho-mediated cell rounding. Activation of Rac may antagonize Rho by regulating phosphorylation of the myosin-II heavy chain. Stimulation of PC12 cells or N1E-115 neuroblastoma cells with bradykinin induces phosphorylation of threonine residues in the myosin-II heavy chain; this phosphorylation is Ca2+ dependent and regulated by Rac. Both bradykinin-mediated and constitutive activation of Rac promote cell spreading, accompanied by a loss of cortical myosin II. These results identify the myosin-II heavy chain as a new target of Rac-regulated kinase pathways, and implicate Rac as a Rho antagonist during myosin-II-dependent cell-shape changes (van Leeuwen, 1999). The molecular events responsible for Rac-mediated cytoskeletal changes are not ...
Risk, Cell, Gene, Potassium, Cells, Hela Cells, Lead, Role, Bradykinin, Action Potential, Adrenoceptors, Emotional Stress, Ether, Human, Inhibition, Ion Channel, Kinase, Myocytes, Phenylephrine, Potassium Channels
INCB 024360 is a potent and selective IDO1 inhibitor with IC50 of 71.8 nM±17.5 nM....Quality confirmed by NMR,HPLC & MS.
Cobimetinib is a novel selective MEK inhibitor, and the IC50 value against MEK1 is 4.2 nM. ...Quality confirmed by NMR,HPLC & MS.
BioAssay record AID 277735 submitted by ChEMBL: Antagonist potency at human bradykinin B2 receptor assessed as effect on inositol monophosphate accumulation in CHOdhfr- cells.
Cardiovascular diseases are a major cause of death in Western countries. Angiotensin-converting enzyme (ACE) is as a key enzyme in the renin-angiotensin system involved in the regulation of blood pressure, and water and electrolyte balance in the body. ACE not ouly increases the conversion of angiotensin I to the active angiotensin II, but also degrades bradykinin. ACE inhibitors, like captopril, are today first-line treatment in hypertension and heart failure.. We have shown that two structurally different ACE inhibitors, captopril and fosinopril, exhibit anti-atherosclerotic effects in hypercholesterolemic mini pigs. Captopril, but not fosinopril, improved endothelial function in the iliac arteries from the mini pigs.. Bradykinin-induced relaxation of porcine iliac arteries was mediated by bradykinin B2 receptors and the subsequent release of nitric oxide (NO). ACE inhibitors did not affect the bradykinin-induced relaxation, implying that other enzymes than ACE (e. g. carboxypeptidase M; CPM) ...
Bradykinin-related peptides (BRPs) are one of the most extensively studied frog secretions-derived peptide families identified from many amphibian species. The diverse primary structures of BRPs have been proven essential for providing valuable information in understanding basic mechanisms associated with drug modification. Here, we isolated, identified and characterized a dodeca-BRP (RAP-L1, T6-BK), with primary structure RAPLPPGFTPFR, from the skin secretions of Chinese large odorous frogs, Odorrana livida. This novel peptide exhibited a dose-dependent contractile property on rat bladder and rat ileum, and increased the contraction frequency on rat uterus ex vivo smooth muscle preparations; it also showed vasorelaxant activity on rat tail artery smooth muscle. In addition, the analogue RAP-L1, T6, L8-BK completely abolished these effects on selected rat smooth muscle tissues, whilst it showed inhibition effect on bradykinin-induced rat tail artery relaxation. By using canonical antagonist for
Retinal Arteriolar Caliber Predicts Incident Retinopathy. Rogers, Sophie Louise; Tikellis, Gabriella; Cheung, Ning; Tapp, Robyn; Shaw, Jonathan; Zimmet, Paul Z.; Mitchell, Paul; Wang, Jie Jin; Wong, Tien Yin // Diabetes Care;Apr2008, Vol. 31 Issue 4, p761 Changes in retinal vascular caliber may reflect subclinical microvascular disease and provide prognostic information regarding risk of retinopathy. In this study, we examined the prospective association of retinal vascular caliber with retinopathy risk in an Australian population-based cohort. A... ...
1) Kininogens are inhibitors of thiol proteases; (2) HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) HMW-kininogen inhibits the thrombin- and plasmin-induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from HMW-kininogen shows a variety of physiological effects: (4A) influence in smooth muscle contraction, (4B) induction of hypotension, (4C) natriuresis and diuresis, (4D) decrease in blood glucose level, (4E) it is a mediator of inflammation and causes (4E1) increase in vascular permeability, (4E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (4F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action); (5) LMW-kininogen inhibits the aggregation of thrombocytes; (6) LMW-kininogen is in contrast to HMW-kininogen not involved in blood clotting. ...
In November 2009, CRD secured DOJs largest ever monetary settlement of rental discrimination claims, requiring owners of numerous apartment buildings in Los Angeles to pay $27 million to Black and Hispanic victims of discrimination seeking rental homes! Until skittishly buy propecia online use (not exceeding a 4-week storage period). What I also find interesting is that Walmart, Kroger, Target still have many of these products (ie? Examples of R 9g groups include substituted and unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclic, aralkyl, and hydrogen! «Lady Gaga Designs Japanese Tsunami Relief Wristband» (en inglés). "Angiotensin-converting enzyme (ACE) 阻害薬誘発性の咳嗽発現とACE 遺伝子型,血漿中ブラジキニン,サブスタンスP 及びACE 阻害薬濃度との関連性" [No Relation between Angiotensin-Converting Enzyme (ACE) Inhibitor-Induced Cough and ACE Gene Polymorphism, Plasma Bradykinin, Substance P and ACE Inhibitor Concentration in Japanese ...
Tissue injury generates endogenous factors that heighten our sense of pain by increasing the response of sensory nerve endings to noxious stimuli. Bradykinin and nerve growth factor (NGF) are two such pro-algesic agents that activate G-protein-coupled (BK2) and tyrosine kinase (TrkA) receptors, respectively, to stimulate phospholipase C (PLC) signalling pathways in primary afferent neurons. How these actions produce sensitization to physical or chemical stimuli has not been elucidated at the molecular level. Here, we show that bradykinin- or NGF-mediated potentiation of thermal sensitivity in vivo requires expression of VR1, a heat-activated ion channel on sensory neurons. Diminution of plasma membrane phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) levels through antibody sequestration or PLC-mediated hydrolysis mimics the potentiating effects of bradykinin or NGF at the cellular level. Moreover, recruitment of PLC-gamma to TrkA is essential for NGF-mediated potentiation of channel ...
Inflammation causes hyperalgesia, an enhanced sensitivity to noxious stimuli. Transient receptor potential vanilloid 1 (TRPV1), a thermo-TRP ion channel activated by painful levels of heat, is an important contributor because hyperalgesia is reduced when TRPV1 is either genetically deleted or pharmacologically blocked. Inflammatory mediators such as prostaglandin-E2 or bradykinin cause hyperalgesia by activating cellular kinases that phosphorylate TRPV1, a process that has recently been shown to rely on a scaffolding protein, AKAP79, to target the kinases to TRPV1. Here we use Forster resonance energy transfer, immunoprecipitation, and TRPV1 membrane trafficking experiments to identify a key region on AKAP79, between amino acids 326-336, which is responsible for its interaction with TRPV1. A peptide identical to this domain inhibited sensitization of TRPV1 in vitro, and when covalently linked to a TAT peptide to promote uptake across the cell membrane the peptide inhibited in vivo inflammatory ...
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Die intestinale Mukosa bildet eine biologisch wichtige Barriere zwischen dem Organismus und den schädigenden Faktoren im intestinalen Lumen. Diese komplexe Aufgabe wird durch eine hochdifferenzierte intestinale Mukosa bewältigt, die eine strukturelle sowie funktionelle intestinale Barriere bildet. Das Ziel der vorliegenden Arbeiten war, ausgewählte Aspekte der Regulations- und Reparaturmechanismen der intestinalen mukosalen Barriere weitergehend zu charakterisieren. Unsere Untersuchungen zeigen, dass das Phospholipid Lysophosphatidsäure (LPA) die intestinale epitheliale Zellmigration stimuliert, die dieser Zellen jedoch inhibiert. Die Modulation der intestinalen Wundheilung durch LPA erfolgt durch einen TGF-b-unabhängigen Mechanismus und wird über einen G-Protein-abhängigen Rezeptor vermittelt, wie wir im Rahmen umfangreicher Untersuchungen zur Signaltransduktion unter Verwendung spezifischer Modulatoren der Signaltransduktion wie Bradykinin, Phorbolester, Pertussistoxin, Suramin und ...
To substrater ble brukt i de eksperimetelle studiene. De er referet til som Bradykinin-lignende substrat og AGLA substrat i oppgaven. De eksperimentelle forsøkene gav Km verdi for Bradykinin lignende substrat for Thermolysin fra Bacillus thermoproteolyticus eubakterie på 17.7 +/- 4.3 μM og Pseudolysin fra Pseudomonas aeruginosa på 7.4 +/- 1.3 μM. For "AGLA" substrat ble Km for Thermolysin målt til 67.7 +/- 10.5 μM, mens for Pseudolysin ble Km målt til 124.8 +/- 22.9 μM. Seksten forbindelser fra en tidligere "virtual screening" studie av Maybridge databasen viste ingen hemmende effekt hverken på verken Thermolysin eller Pseudolysin. Både under preinkubering av hemmere og under alle forsøk var pH 7.3, mens temperaturen var 37 °C. Av totalt 50 forbindelser (42+8) fra samarbeidspartnere i Italia, viste forbindelse FF33 en IC50 på 754 nM mot Thermolysin og IC50 på 2.28 μM mot Pseudolysin. Forbindelse VDL22 hadde en IC50 på 11,14 μM mot Thermolysin. Forbindelse SM434 viste seg å ...
MK-1775 is a potent and selective Wee1 inhibitor with IC50 of 5.2 nM in a cell-free assay; hinders G2 DNA damage checkpoint. Phase 2.
Title:Kinin Receptors in Vascular Biology and Pathology. VOLUME: 12 ISSUE: 2. Author(s):Rejean Couture, Nelly Blaes and Jean-Pierre Girolami. Affiliation:Department of Physiology, Faculty of Medicine, Universite de Montreal, C. P. 6128, Succursale Centre- Ville, Montreal (Quebec) Canada, H3C 3J7.. Keywords:ACEI, AT1 receptor blockers, bradykinin, B1-kinin receptor, B2-kinin receptor, diabetes mellitus, endothelium, inflammation, ischemia, nitric oxide, oxidative stress.. Abstract:Endogenous kinins are important vasoactive peptides whose effects are mediated by two G-Protein-coupled receptors (R), named B2R (constitutive) and B1R (inducible). They are involved in vascular homeostasis, ischemic pre- and post- conditioning, but also in cardiovascular diseases. They contribute to the therapeutic effects of angiotensin-1 converting enzyme inhibitors (ACEI) and angiotensin AT1 receptor blockers. Benefits derive primarily from vasodilatory, antiproliferative, antihypertrophic, antifibrotic, ...
Bradykinin and phorbol 12-myristate 13-acetate stimulate adenylate cyclase activity in serum-depleted cultured airway smooth muscle via a protein kinase C (PKC)-dependent pathway. The probable target is the type II adenylate cyclase, which can integrate coincident signals from both PKC and Gs. Therefore, activation of Gs (by cholera-toxin pre-treatment) amplified the bradykinin-stimulated cyclic AMP signal and concurrently attenuated the partial activation of extracellular-signal-regulated kinase-2 (ERK-2) by bradykinin. We have previously demonstrated that, in order to induce full activation of ERK-2 with bradykinin, it is necessary to obliterate PKC-stimulated cyclic AMP formation. We concluded that the cyclic AMP signal limits the magnitude of ERK-2 activation [Pyne, Moughal, Stevens, Tolan and Pyne (1994) Biochem. J. 304, 611-616]. The present study indicates that the bradykinin-stimulated ERK-2 pathway is entirely cyclic AMP-sensitive, and suggests that coincident signal detection by ...
L-Citrulline was measured by high-performance liquid chromatography in 250 coronary effluent samples from 32 hearts before and during exposure to each anesthetic in the absence and presence of 0.1, 1, 10, and 100 nM bradykinin. The high-performance liquid chromatography system consisted of a Laboratory Data Control constametric III G pump (Rivera Beach, FL), a Gilson Automatic Sampler model 231 (Middletown, WI), and an electrochemical detector (BAS LC-4B; Bioanalytical Systems, West Lafayette, IN). The column (Beckman Ultrasphere ODS 5 [micro sign], 4.6 mm x 25 cm, Fullerton, CA) was perfused at a mobile phase flow rate of 1.5 ml/min. The detector potential was set at +0.7 V. The mobile phase consisted of 800 ml 0.1 M sodium acetate, adjusted to pH 5.7, plus 260 ml acetonitrile. L-Citrulline was detected electrochemically as the o-phthaldialdehyde derivative. The o-phthaldialdehyde reagent consisted of 25 ml 0.1 M borate buffer (pH 9.5), 50 [micro sign] 2-methyl 2-propanethiol, 2.5 ml methanol, ...
... : Schematic presentation of PRCP roles in mammals This schematic presentation highlights major cell functions, which are regulated by PRCP following stimulation by hormones, neuromediators, or drugs. It appears that PRCP is highly regulated and the target of pharmaceutical intervention. AT2; angiotensin II type 2 receptor, SHP-1; sarcoma homology region 2 domain-containing phosphatase 1 (also known as tyrosin protein phosphatase type 6), LC3-2; microtubule-associated protein 1 light chain 3 type 2, BK; bradykinin, KLF2; Krueppel-like factor 2, eNOS; endothelial nitric oxide synthase, B2; bradykinin B2 receptor, MasR; Mas 1 oncogene, α-MSH; alpha melanocyte stimulating hormone, IL; interleukin, TNF-α; tumor necrosis factor alpha, IFN-γ; interferon gamma, and ICAM-1; intracellular Adhesion molecule 1 ...
Icatibant may cause potentially serious reactions, allergic reactions, or other problems in some people. This eMedTV Web page examines other possible side effects of icatibant and explains which problems require urgent medical attention.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Croxatto, H.R., Huidobro, F., Croxatto, R. et Salvestrini, H., Action cholinestérasique du sang veineux pendant lexcitation musculaire directe et indirecte, Compt. Rend. Seanc. Soc. Biol. Paris, 130, p. 326 (1939); Croxatto, H.R. and Croxatto, R., Pepsitensin - A hypertensin-like substance produced by peptidic digestion of proteins, Science, 95, p. 101 (1942); Croxatto, H.R., Rojas, G. and Barnafi, L., The liberation of antidi- uretic factor by the hypertensinogen pepsin reaction, Acta Physiol. Latinoamer., 2, p. 178 (1951); Croxatto, H.R., Pereda, T. and Mellada, R., Peptides with oxytocin and pressor activity obtained from acidified rat serum, Nature, 184, p. 1496 (1959); Croxatto, H.R. and Barnafi, L., Hormone and hormone-like activity of active polypeptides, Rec. Prog. Horm. Res., 16, p. 236 (1961); Croxatto, H.R. and Belmar, J., Hypertensive effects of bradykinin in rats, Nature, 192 (4805), p. 879 (1961); Croxatto, H.R., Pereda, T., Belmar, J. and Labarca, E., Polypeptides ...
TY - JOUR. T1 - Mechanism of bradykinin-induced histamine release from rat peritoneal mast cells. AU - Zhao, Qiu E.. AU - Mihara, Takuma. AU - Sugimoto, Yukio. AU - Kamei, Chiaki. PY - 1996/2. Y1 - 1996/2. N2 - Bradykinin at concentrations higher than 2 μM caused a significant histamine release from rat peritoneal mast cells when extracellular Ca2+ was removed from the medium. Under the same experimental conditions, bradykinin increased Ca2+ release from the intracellular Ca store of the rat peritoneal mast cells, and a clear relationship was observed between the magnitude of histamine release and an increase in fluorescence intensity. Addition of Ca2+ to the medium resulted in an inhibition of the response to bradykinin in a concentration-dependent manner. Almost the same results were obtained when Mg2+, Ba2+ and La3+ were added to the medium. Neither B1 nor B2 antagonists caused significant antagonistic effects on histamine release induced by bradykinin. However, B2 antagonists caused a ...
Figure 1: Bradykinin metabolism and its relationship with two other vasoactive mediators: angiotensin and natriuretic peptides. ACE, angiotensin-converting enzyme; AI, angiotensin I; AII, angiotensin II; ANP, atrial natriuretic peptide; APP, aminopeptidase P; AT1, angiotensin II type I receptor; AT2, angiotensin II type II receptor; BK, bradykinin; BNP, brain natriuretic peptide; CNP, C-natruretic peptide; NEP, neutral endopeptidase 24.11; NPR-A, natriuretic peptide receptor type A; NPR-B, natriuretic peptide receptor type B ...
Coughing is a distressing symptom which has a major impact on quality of life. It has been estimated that cough costs the UK economy £1 billion each year. Currently there are no effective anti-tussive agents to treat subjects with cough. Although drugs such as morphine may have some anti-tussive effect, side effects unacceptable.. Currently our understanding of the mechanisms which lead to coughing in different diseases is poor. Many mechanistic studies rely on testing the sensitivity of the cough reflex by inhalation of capsaicin (chilli-pepper extract) or citric acid. These challenges do not differentiate well between health and disease or between different disease states. Other agents such as prostaglandins and bradykinin are known to stimulate a coughing but responses to these agents have rarely been used as a measure of cough reflex sensitivity and not been compared to standard challenges.. It is clear that patients with common airway diseases such as COPD and asthma cough significantly ...
Role of the kallikrein-kinin system in the renal effects of angiotensin-converting enzyme inhibition in anaesthetized dogs.: 1. Administration of captopril (1.5
Previous studies have shown that local selective in situ injury of pial arteriolar endothelium eliminates the dilations produced by acetylcholine or bradykinin. One means of producing such injury employs a helium-neon laser in the presence of intravascular Evans blue. Since the endothelium-dependent dilations produced by acetylcholine or bradykinin may be initiated by interaction with endothelial surface receptors, it is possible that the light simply inactivates or destroys these receptors. We used calcium ionophore A-23187, another dilating agent known from in vitro studies of large arteries to be endothelium-dependent, which moves calcium into endothelial cells rather than interacting with surface receptors. Our data in 10 mice show that before injury, 10(-5)M A-23187 dilated arterioles to 109 +/- 2% of control diameter. After selective endothelial injury by helium-neon laser, dilation was essentially abolished (101 +/- 1% of baseline diameter; p less than 0.01, Wilcoxon test). Undamaged ...
Yellow, cancerous tumors of hormone-making cells in the gastrointestinal tract (specifically, they are classed as neuroendocrine or amine precursor uptake and decarboxylation tumors). They produce excess endocrines such as kallikrein (an activator of bradykinin release) and serotonin. These tumors can be found in the intestine, stomach, or sometimes on the liver. In later stages, this type of cancer causes symptoms such as diarrhea, wheezing, heart murmurs, enlarged liver, and a dusky appearance to the skin. Carcinoids can be diagnosed with a urine test or with a CAT scan ...
In ischemia, the heart generates and releases kinins as mediators that seem to have cardioprotective actions. Kinin-generating pathways are present in the heart. Kininogen, kininogenases, kinins, and B2 kinin receptors can be measured in cardiac tissue. Kinins are released under conditions of ischemia. In anesthetized rats and dogs with coronary artery ligation and in human patients with myocardial infarction, kinin plasma levels are increased. In isolated rat hearts, the outflow of kinins is enhanced during ischemia but markedly attenuated after deendothelialization, pointing to the coronary vascular endothelium as the main possible source. Kinins administered locally exert beneficial cardiac effects. In isolated rat hearts with ischemia-reperfusion injuries, perfusion with bradykinin (BK) reduces the duration and incidence of ventricular fibrillation, improves cardiodynamics, reduces release of cytosolic enzymes, and preserves energy-rich phosphates and glycogen stores. In anesthetized ...
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The BK1 file. We collected the information you should know about the .BK1 file on this page. If you were sent a .BK1 file in an e-mail, but you dont know what to do with it, then you can find help here.
Kinins (bradykinin, kallidin and their active metabolites) are peptide autacoids with established functions in cardiovascular homeostasis, contraction and relaxation of smooth muscles, inflammation and nociception. They are believed to play a role in disease states like asthma, allergies, rheumatoid arthritis, cancer, diabetes, endotoxic and pancreatic shock, and to contribute to the therapeutic effects of ACE inhibitors in cardiovascular diseases. Although kinins are also neuromediators in the central nervous system, their involvement in neurological diseases has not been intensively investigated thus far. This review analyzes the potential of central kinin receptors as therapeutic targets for neurological disorders. Initial data highlight potential roles for B1 receptor antagonists as antiepileptic agents, and for B2 receptor antagonists (and/or B1 agonists) in the treatment of stroke. Functional B1 receptors located on T-lymphocytes and on the blood brain-barrier are also putative targets for ...
Airway hyperreactivity (AHR) is a major feature of asthmatic and inflammatory airways. Cigarette smoke exposure, and bacterial and viral infections are well-known environmental risk factors for AHR, but knowledge about the underlying molecular mechanisms on how these risk factors lead to the development of AHR is limited. Activation of intracellular mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) and their related signal pathways including protein kinase C (PKC), phosphoinositide 3-kinase (PI3K) and protein kinase A (PKA) signaling pathways may result in airway kinin receptor upregulation, which is suggested to play an important role in the development of AHR. Environmental risk factors trigger the production of pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukins (ILs) that activate intracellular MAPK- and NF-κB-dependent inflammatory pathways, which subsequently lead to AHR via kinin receptor upregulation. Blockage of intracellular ...
The TheraSorb® LDL therapy system consists of two reusable adsorbers, available in different sizes, that remove LDL cholesterol, Lp(a) and VLDL from the patient´s blood. The sepharose volume constituting the adsorbers is 100 mL for the LDL pro adsorber and 200 mL for the LDL adsorber. The plasma volumes processed during an LDL apheresis treatment can be adjusted to the patient´s need. Between the treatments, both adsorbers are stored in a preservation solution and must be kept at 2-8 °C. Up to 20 treatments can be performed with a single pair of either LDL pro or LDL adsorbers for one patient. The treatment is well tolerated due to the low bradykinin release, which otherwise can cause severe hypotension. Furthermore, the low extracorporeal volume of about 180 mL allows for the treatment of patients with a low body weight in double-needle mode. TheraSorb LDL removal is a highly selective procedure. - Suomi
Hereditary angioedema (HAE) is an inherited disorder caused by a specific mutation in the affected persons genetic code. The gene in question is located on chromosome 11 and is responsible for the production of an enzyme known as C1-esterase inhibitor (C1-INH). C1-INH is an important protein that regulates a variety of metabolic processes in the body. As a result of the underlying genetic mutation, persons suffering from HAE either produce too little C1-INH or a type of C1-INH that does not function properly. One of the effects of C1-INH is to prevent an excessive production of bradykinin in response to inflammation, coagulation reactions and other processes in the body. Bradykinin acts to increase the permeability of the blood vessel walls ...
Northern short-tailed shrew by Giles Gonthier; Mexican beaded lizard by PiccoloNamek. The northern short-tailed shrew is one of the few venomous mammals, but its poisonous bite is painful to humans and can kill smaller animals. The key to its venom is a protein called BLTX, whose job is to cut another protein in two. This chemical reaction frees a molecule called bradykinin, which widens blood vessels and lowers blood pressure. Its a necessary job, but BLTX is so active that if floods the body with bradykinin - an overdose that leads to paralysis and death. BLTX is a dark, hyperactive descendant of an ancestral protein called kallikrein-1, which does the same thing but in a much more restrained way. Aminetzach found that BLTX is a longer version of kallikrein and the extra amino acids it has gained have changed the structure of the proteins active site. The active site is the proteins business end - it allows BLTX to latch onto the right targets and catalyse the relevant chemical reactions. ...
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My research interests are to investigate the mechanisms of cardiac sympathetic afferents activation and the associated central nervous system (CNS) reflex processing as well as modulation of electroacupuncture (EA) on CNS regulation of cardiovascular function. Studies of cardiac afferents activation are funded by a NIH grant (serve as CO-PI ). In these studies, I am investigating the mechanisms of activation and sensitization of cardiac afferents induced by multiple ischemic mediators including endothelins, thromboxane A2, 5-hydroxytryptamine (5-HT), histamine, lactic acid (protons), reactive oxygen species and bradykinin (BK), which stimulate and/or sensitize cardiac spinal afferents during ischaemia and reperfusion in an interactive and multifactorial fashion. I am also studying the mechanisms underlying CNS reflex processing evoked by ischemic metabolites during myocardial ischemia ...
Angiotensin I, Bradykinin, Active Sites, Angiotensin, Angiotensin I-converting Enzyme, Binding Site, Blood, Blood Pressure, Captopril, Casein, Catalytic Domains, Food, Human, Hypertension, Ic50, Lisinopril, Plays, Pressure, Regression, Regression Analysis
In our previous work beta-endorphin, morphine, and d-ala2-met-enkephalinamide in the nanomolar range were found to produce preferential vasodepressor responses and bradycardia upon intracisternal (i....
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Abstract: In experimental myocardial infarction in dogs even within first minutes after occlusion of coronary artery content of bradikinine was distinctly decreassed in blood plasma, content of kallikrein was increased and the activity of kininase was decreased in blood. These phenomena reflected the activation of kallikrein-kinin system. An increase in content of glutamate-oxaloacetate transaminase was observed only within 6 hrs after ligation of the coronary artery. Content of adrenaline and noradrenaline was increased in the zone of myocardial infarction within 2 days after the onset of the disease; content of the catecholamines was significantly increased (3-17-fold) in adrenal glands. In acute period of myocardial infarction intravenous administration of adrenaline into animals caused a promt, distinct kininogenolytic effect and increased the content of kallikrein in blood. These findings demonstrate a significant effect of adrenaline on kallikrein-kinin system ...
In previous studies it has been shown that both bradykinin and histamine increase the formation of H-3-labeled inositol phosphates in adrenal chromaffin cells prelabelled with [H-3]inositol and that both these agonists stimulate release of catecholamines by a mechanism dependent on extracellular calcium. Here, we have used mass assays of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] to investigate changes in levels of these two candidates as second messengers in response to stimulation with bradykinin and histamine. Bradykinin increased the mass of Ins(1,3,4,5)P4 despite the failure in earlier studies with [H-3]inositol-labelled cells to observe a bradkinin-mediated increase in content of [H-3]InsP4. Bradykinin elicited a very rapid increase in level of Ins(1,4,5)P3, which was maximal at 5-10 s and then rapidly decreased to a small but sustained elevation at 2 min. The bradykinin-elicited Ins(1,3,4,5)P4 response increased to a maximum at ...
To date there has been a paucity of animal models in which the role of the plasma KKS can be studied. One such model is the bradykinin B2 receptor knockout mouse (BKB2R-/-). Mice with this defect have cardiac hypertrophy, chamber dilatation, and elevated left ventricular end-diastolic pressure, and they show exaggerated vasopressor responses to angiotensin II (23). In the presence of angiotensin II infusion, these animals have increased blood pressure and reduced renal blood flow (24). They also experience a diminished cardioprotective benefit from angiotensin I receptor antagonists and angiotensin-converting enzyme inhibitors, relative to the response of wild-type mice after ischemia-induced heart failure (25). This animal model links bradykinin with angiotensin II in the development of cardiac disease, but leaves open the question of their interrelationship in the area of thrombosis, where the expected phenotype is by no means obvious. While it is possible that the BKB2R-/- mouse will prove to ...
Although we found that the vasoconstrictor response to l-NMMA was lower in blacks, we did not examine effects of other nonspecific vasoconstrictors to investigate whether this is a reflection of reduced sensitivity of the vascular smooth muscle to vasoconstrictors. However, the fact that the constrictor response to TEA was similar to whites suggests that the response to l-NMMA is specific for reduced NO bioavailability. The reduced sensitivity to exogenous NO (sodium nitroprusside) complicates the interpretation of the reduced dilator responses observed with acetylcholine and bradykinin in blacks. However, because basal NO and the contribution of NO during exercise is lower in blacks, it is likely that in addition to reduced sensitivity, there is also an endothelial defect in NO release in blacks.. l-NMMA and TEA are competitive inhibitors, and thus our results may underestimate the physiological contribution of both NO and K+Ca channels to vasodilation. Our investigation was conducted on a ...
Hereditary angioedema (HAE) due to C1 esterase inhibitor (C1-INH) deficiency (HAE-C1-INH) is a rare but medically significant disease that can be associated with considerable morbidity and mortality. Research into the pathogenesis of HAE-C1-INH has expanded greatly in the last six decades and has led to new clinical trials with novel therapeutic agents and treatment strategies. Mechanisms of pharmacotherapy include (a) supplementing C1-INH, the missing serine-protease inhibitor in HAE; (b) inhibiting the activation of the contact system and the uncontrolled release of proteases in the kallikrein-kinin system, by blocking the production/function of its components; (c) inhibiting the fibrinolytic system by blocking the production/function of its components; and (d) inhibiting the function of bradykinin at the endothelial level ...
The aim of this study was to characterise vasodilator responses in the perfused ciliary vascular bed of the bovine eye. When bovine eyes were perfused at a constant rate of 2.5 ml min-1, infusion of the powerful vasodilator, papaverine (150 muM), produced a very small reduction in perfusion pressure. Under the same conditions, the nitric oxide synthase inhibitor, L- NAME (100 muM), had no effect but the inhibitor of soluble guanylate cyclase, ODQ (10 muM), produced a small vasoconstrictor response. These results indicate that there is a small component of intrinsic (myogenic) tone that may be suppressed by a basal release of nitric oxide. In the bovine eye, vasodilatation to acetylcholine or bradykinin was unaffected by L- NAME (100 muM), or the cyclo-oxygenase inhibitor, flurbiprofen (30 muM), but was significantly attenuated following treatment with a high concentration of KC1 (30 muM), or by damaging the endothelium with the detergent, CHAPS (0.3%, 2 min). Thus agonist-induced vasodilatation ...
... is an aminonucleoside antibiotic, derived from the Streptomyces alboniger bacterium,[1] that causes premature chain termination during translation taking place in the ribosome. Part of the molecule resembles the 3' end of the aminoacylated tRNA. It enters the A site and transfers to the growing chain, causing the formation of a puromycylated nascent chain and premature chain release.[2] The exact mechanism of action is unknown at this time but the 3' position contains an amide linkage instead of the normal ester linkage of tRNA. That makes the molecule much more resistant to hydrolysis and stops the ribosome. Puromycin is selective for either prokaryotes or eukaryotes. Also of note, puromycin is critical in mRNA display. In this reaction, a puromycin molecule is chemically attached to the end of an mRNA template, which is then translated into protein. The puromycin can then form a covalent link to the growing peptide chain allowing the mRNA to be physically linked to its translational ...
... (GLP-2) is a 33 amino acid peptide with the sequence HADGSFSDEMNTILDNLAARDFINWLIQTKITD (see Proteinogenic amino acid) in humans. GLP-2 is created by specific post-translational proteolytic cleavage of proglucagon in a process that also liberates the related glucagon-like peptide-1 (GLP-1). GLP-2 is produced by the intestinal endocrine L cell and by various neurons in the central nervous system. Intestinal GLP-2 is co-secreted along with GLP-1 upon nutrient ingestion. When externally administered, GLP-2 produces a number of effects in humans and rodents, including intestinal growth, enhancement of intestinal function, reduction in bone breakdown and neuroprotection. GLP-2 may act in an endocrine fashion to link intestinal growth and metabolism with nutrient intake. GLP-2 and related analogs may be treatments for short bowel syndrome, Crohn's disease, osteoporosis and as adjuvant therapy during cancer chemotherapy. ...
Cholecystokinin tetrapeptide (CCK-4, Trp-Met-Asp-Phe-NH2) is a peptide fragment derived from the larger peptide hormone cholecystokinin. Unlike cholecystokin which has a variety of roles in the gastrointestinal system as well as central nervous system effects, CCK-4 acts primarily in the brain as an anxiogenic, although it does retain some GI effects, but not as much as CCK-8 or the full length polypeptide CCK-58. CCK-4 reliably causes severe anxiety symptoms when administered to humans in a dose of as little as 50μg,[1] and is commonly used in scientific research to induce panic attacks for the purpose of testing new anxiolytic drugs.[2][3][4][5] Since it is a peptide, CCK-4 must be administered by injection, and is rapidly broken down once inside the body so has only a short duration of action,[6] although numerous synthetic analogues with modified properties are known.[7][8][9][10][11][12][13][14][15][16][17] ...
... (INN) (code name MK-0974) is a calcitonin gene-related peptide receptor antagonist which was an investigational drug for the acute treatment and prevention of migraine, developed by Merck & Co..[1] In the acute treatment of migraine, it was found to have equal potency to rizatriptan[2] and zolmitriptan[3] A Phase IIa clinical trial studying telcagepant for the prophylaxis of episodic migraine was stopped on March 26, 2009 after the "identification of two patients with significant elevations in serum transaminases".[4] A memo to study locations stated that telcagepant had preliminarily been reported to increase the hepatic liver enzyme alanine transaminase (ALT) levels in "11 out of 660 randomized (double-blinded) study participants." All study participants were told to stop taking the medication.[5] On July 2011, Merck announced that it had discontinued development of telcagepant.[6] ...
The neuropeptide galanin elicits a range of biological effects by interaction with specific G-protein-coupled receptors. Galanin receptors are seven-trans membrane proteins shown to activate a variety of intracellular second-messenger pathways. GALR1 inhibits adenylyl cyclase via a G protein of the GI/GO family. GALR1 is widely expressed in the brain and spinal cord, as well as in peripheral sites such as the small intestine and heart.[5]. ...
Bradykinins. Tachykinins: mammal *Substance P. *Neurokinin A. *Neurokinin B. amphibian *Kassinin. *Physalaemin ...
Bradykinins. Tachykinins: mammal *Substance P. *Neurokinin A. *Neurokinin B. amphibian *Kassinin. *Physalaemin ...
... s (from Gr.: πεπτός, peptós "digested"; derived from πέσσειν, péssein "to digest") are short chains of amino acid monomers linked by peptide (amide) bonds.. The covalent chemical bonds are formed when the carboxyl group of one amino acid reacts with the amino group of another. The shortest peptides are dipeptides, consisting of 2 amino acids joined by a single peptide bond, followed by tripeptides, tetrapeptides, etc. A polypeptide is a long, continuous, and unbranched peptide chain. Hence, peptides fall under the broad chemical classes of biological oligomers and polymers, alongside nucleic acids, oligosaccharides and polysaccharides, etc.. Peptides are distinguished from proteins on the basis of size, and as an arbitrary benchmark can be understood to contain approximately 50 or fewer amino acids.[1][2] Proteins consist of one or more polypeptides arranged in a biologically functional way, often bound to ligands such as coenzymes and cofactors, or to another protein or ...
... , also called chorionic somatomammotropin, is a polypeptide placental hormone, part of the somatotropin family. Its structure and function is similar to that of growth hormone. It modifies the metabolic state of the mother during pregnancy to facilitate the energy supply of the fetus. For information on the human form, see human placental lactogen. Placental lactogen I and II were identified as prolactin-like molecules that can bind to prolactin receptor with high affinity and mimic the actions of prolactin. These hormones can contribute to lactogenesis, luteal maintenance and progesterone production (in rats) during the later stages of gestation. Placental lactogen I may be important in stimulating mammary cell proliferation and in stimulating some of the adaptations of the maternal lipid and carbohydrate metabolism. ...
Many kinds of peptides are known. They have been classified or categorized according to their sources and function. According to the Handbook of Biologically Active Peptides, some groups of peptides include plant peptides, bacterial/antibiotic peptides, fungal peptides, invertebrate peptides, amphibian/skin peptides, venom peptides, cancer/anticancer peptides, vaccine peptides , immune/inflammatory peptides, brain peptides, endocrine peptides, ingestive peptides, gastrointestinal peptides, cardiovascular peptides, renal peptides, respiratory peptides, opiate peptides, neurotrophic peptides, and blood-brain peptides.[5] Some ribosomal peptides are subject to proteolysis. These function, typically in higher organisms, as hormones and signaling molecules. Some organisms produce peptides as antibiotics, such as microcins.[6] Peptides frequently have posttranslational modifications such as phosphorylation, hydroxylation, sulfonation, palmitoylation, glycosylation and disulfide formation. In general, ...
The human CRHR2 gene contains 12 exons. Three major functional isoforms, alpha (411 amino acids), beta (438 amino acids), and gamma (397 amino acids), encoded by transcripts with alternative first exons,[7] differ only in the N-terminal sequence comprising the signal peptide and part of the extracellular domain (amino acids 18-108 of CRHR2 alpha); the unique N-terminal sequence of each isoform (34 amino acids in CRHR2 alpha; 61 amino acids in Hs CRHR2 beta; 20 amino acids in CRHR2 gamma) is followed by a sequence common to all isoforms (377 amino acids)[8] comprising most of the multi-pass transmembrane domain followed by a cytoplasmic domain of 47 amino acids. CRHR2 beta is expressed in human brain; CRHR2 alpha predominates in peripheral tissues. The N-terminal signal peptides of corticotropin-releasing hormone receptor 1 and CRHR2 beta are cleaved off in the endoplasmic reticulum to yield the mature receptors. In contrast, CRHR2 alpha contains a unique pseudo signal peptide that is not removed ...
Toy-Miou-Leong M, Cortes CL, Beaudet A, Rostène W, Forgez P (Mar 2004). "Receptor trafficking via the perinuclear recycling compartment accompanied by cell division is necessary for permanent neurotensin cell sensitization and leads to chronic mitogen-activated protein kinase activation". The Journal of Biological Chemistry. 279 (13): 12636-46. doi:10.1074/jbc.M303384200. PMID 14699144 ...
ProIAPP has been linked to Type 2 diabetes and the loss of islet β-cells.[24] Islet amyloid formation, initiated by the aggregation of proIAPP, may contribute to this progressive loss of islet β-cells. It is thought that proIAPP forms the first granules that allow for IAPP to aggregate and form amyloid which may lead to amyloid-induced apoptosis of β-cells. IAPP is cosecreted with insulin. Insulin resistance in Type 2 diabetes produces a greater demand for insulin production which results in the secretion of proinsulin.[25] ProIAPP is secreted simultaneously, however, the enzymes that convert these precursor molecules into insulin and IAPP, respectively, are not able to keep up with the high levels of secretion, ultimately leading to the accumulation of proIAPP. In particular, the impaired processing of proIAPP that occurs at the N-terminal cleavage site is a key factor in the initiation of amyloid.[25] Post-translational modification of proIAPP occurs at both the carboxy terminus and the ...
Bradykinins. Tachykinins: mammal *Substance P. *Neurokinin A. *Neurokinin B. amphibian *Kassinin. *Physalaemin ...
CCK receptors significantly influence neurotransmission in the brain, regulating anxiety, feeding, and locomotion. CCK-B expression may correlate parallel to anxiety and depression phenotypes in humans. CCK-B receptors possess a complex regulation of dopamine activity in the brain. CCK-B activation appears to possess a general inhibitory action on dopamine activity in the brain, opposing the dopamine-enhancing effects of CCK-A. However, the effects of CCK-B on dopamine activity vary depending on location.[11] CCK-B antagonism enhances dopamine release in rat striatum.[12] Activation enhances GABA release in rat anterior nucleus accumbens.[13] CCK-B receptors modulate dopamine release, and influence the development of tolerance to opioids.[14] CCK-B activation decreases amphetamine-induced DA release, and contributes to individual variability in response to amphetamine.[15] In rats, CCK-B antagonism prevents the stress-induced reactivation of cocaine-induced conditioned place preference, and ...
The package insert for Gonal-F states that based on physio-chemical tests and bioassays that follitropin beta and follitropin alfa are indistinguishable. Two studies showed no difference.[5][6] However, a more recent study showed there may be a slight clinical difference, with the alfa form tending towards a higher pregnancy rate and the beta form tending towards a lower pregnancy rate, but with significantly higher estradiol (E2) levels.[7]. The package insert for Puregon states that structural analysis shows that the amino acid sequence of follitropin beta is identical to that of natural human follicle stimulating hormone (hFSH). Further, the ogliosaccharide side chains are very similar, but not completely identical to that of natural hFSH. However, these small differences do not affect the bioactivity compared to natural hFSH.. ...
PTHrP is related in function to the "normal" parathyroid hormone. When a tumor secretes PTHrP, this can lead to hypercalcemia.[7] As this is sometimes the first sign of the malignancy, hypercalcemia caused by PTHrP is considered a paraneoplastic phenomenon. PTHR1 is responsible for most cases of humoral hypercalcemia of malignancy. PTHrP shares the same N-terminal end as parathyroid hormone and therefore it can bind to the same receptor, the Type I PTH receptor (PTHR1). PTHrP can simulate most of the actions of PTH including increases in bone resorption and distal tubular calcium reabsorption, and inhibition of proximal tubular phosphate transport. However, PTHrP is less likely than PTH to stimulate 1,25-dihydroxyvitamin D production. Therefore, PTHrP does not increase intestinal calcium absorption. ...
In industry, EDTA is mainly used to sequester metal ions in aqueous solution. In the textile industry, it prevents metal ion impurities from modifying colors of dyed products. In the pulp and paper industry, EDTA inhibits the ability of metal ions, especially Mn2+, from catalyzing the disproportionation of hydrogen peroxide, which is used in chlorine-free bleaching. In a similar manner, EDTA is added to some food as a preservative or stabilizer to prevent catalytic oxidative decoloration, which is catalyzed by metal ions.[4] In soft drinks containing ascorbic acid and sodium benzoate, EDTA mitigates formation of benzene (a carcinogen).[5] The reduction of water hardness in laundry applications and the dissolution of scale in boilers both rely on EDTA and related complexants to bind Ca2+, Mg2+, as well as other metal ions. Once bound to EDTA, these metal centers tend not to form precipitates or to interfere with the action of the soaps and detergents. For similar reasons, cleaning solutions often ...
Histamine, Bradykinin, and Their Antagonists". In Brunton L. Goodman & Gilman's The Pharmacological Basis of Therapeutics (12e ...
Dampening or inhibiting bradykinin has been shown to relieve HAE symptoms. Various mechanisms that interfere with bradykinin ... ACE inhibitors block the enzyme ACE so it can no longer degrade bradykinin; thus, bradykinin accumulates and causes angioedema ... ACE inhibitors block ACE, the enzyme that among other actions, degrades bradykinin. In hereditary angioedema, bradykinin ... In those with bradykinin related disease a C1 esterase inhibitor, ecallantide, or icatibant may be used. Fresh frozen plasma ...
It inactivates bradykinin and anaphylatoxins. Plummer, T.H. Jr.; Erdös, E.G. (1981). "Human plasma carboxypeptidase N". Methods ... bradykinin-decomposing enzyme, protaminase, CPase N, creatinine kinase convertase, peptidyl-L-lysine(-L-arginine) hydrolase, ...
The converting enzyme also inactivates bradykinin. Circulation time through the alveolar capillaries is less than one second, ...
Maurício Rocha e Silva, the discoverer of bradykinin. While working on this subject, he discovered a family of peptides present ... This factor was named bradykinin potentiating factor, BPF. In 1968, with the collaboration of Dr. Lewis Joel Greene, from the ... His group made a relevant contribution to the role of bradykinin and of cytokines in the development of inflammatory ... Bradykinin initiates cytokine mediated inflammatory hyperalgesia. Brazilian Journal of Pharmacological Sciences. vol. 110, p. ...
"Pro-carboxypeptidase R cleaves bradykinin following activation". Int. Arch. Allergy Immunol. 103: 400-404. doi:10.1159/ ...
HMWK is also a precursor of bradykinin; this vasodilator is released through positive feedback by kallikrein. HMWK is a strong ... and in the generation of the vasodilator bradykinin via the Kallikrein-kinin system. HMWK is inactive until it either adheres ... bradykinin generation Domain 5 - heparin and cell binding; antiangiogenic properties; binding to negatively charged surfaces ...
Bradykinins. Tachykinins: mammal *Substance P. *Neurokinin A. *Neurokinin B. amphibian *Kassinin. *Physalaemin ...
... the attenuation of vasodilation in response to bradykinin can best be explained by alterations relating to the bradykinin B2 ... Dilation to A23187 but not bradykinin or 2-Fly can be inhibited by Ba2+ (30 μmol/L) plus ouabain (10 μmol/L; Smeda J, McGuire J ... The levels of constriction in response to pressure (Figure 6A, c versus d) or vasodilation in response to bradykinin (Figure 6C ... Losartan is also capable of restoring both PDC and bradykinin vasodilation in the MCAs of SHRsp after as little as 7 days of ...
The accumulated bradykinin activates Sertoli cell function, regulates spermatogenesis, and leads to the maturation of ... ACE inhibitor improves insulin resistance in diabetic mouse via bradykinin and NO. Hypertension 2002, 40, 329-334. [Google ... ACEIs exert beneficial effects on the sperm quantity and quality by blocking the conversion of bradykinin in the related ...
Whether increased levels of bradykinin, a potent vasopressor peptide, play a role in the therapeutic effects of Ramipril ... Angiotensin converting enzyme is identical to kininase, an enzyme that degrades bradykinin. ...
Bradykinin is a 9-amino acid peptide chain. The amino acid sequence of bradykinin is: Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg ( ... Main article: Bradykinin receptor. *The B1 receptor (also called bradykinin receptor B1) is expressed only as a result of ... Bradykinins have been implicated in a number of cancer progression processes.[16] Increased levels of bradykinins resulting ... they discovered the powerful hypotensive effects of bradykinin in animal preparations. Bradykinin was detected in the blood ...
Several Authors have demonstrated the occurrence of bradykinin in tissues affected by allergic and inflammatory processes: this ... GJURIS V., HEICKE B. and WESTERMANN E. (1964) - Uber die Stimulie rung der Atmung durch Bradykinin und Kallidin - Arch. Exper. ... Della Bella D., Benelli G., Pajola E., Valli P. (1972) Bronchial Motility Regulation and Bradykinin. In: Back N., Sicuteri F. ( ... SICUTERI F., FANCIULLACCI M., FRANCHI G. and DEL BIANCO P.L. (1965) - Serotonin-bradykinin potentiation on the pain receptors ...
There are two Bradykinin receptors: the B1 receptor and the B2 receptor. Bradykinin receptor B1 (B1) is a G-protein coupled ... The bradykinin receptor family is a group of G-protein coupled receptors whose principal ligand is the protein bradykinin. ... The B1 receptor is one of two G protein-coupled receptors that have been found which bind bradykinin and mediate responses to ... "Bradykinin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. ...
... Jagdish N. Sharma Department of Applied Therapeutics, Faculty of ...
... is a mixture of snake venom peptides which potentiate some of the pharmacological actions of bradykinin in vitro and in vivo( ... Bradykinin-potentiating factor (BPF) is a mixture of snake venom peptides which potentiate some of the pharmacological actions ... In: Sicuteri F., e Silva M.R., Back N. (eds) Bradykinin and Related Kinins. Advances in Experimental Medicine and Biology, vol ... Greene L.J., Stewart J.M., Ferreira S.H. (1970) Bradykinin-Potentiating Peptides from the Venom of Bothrops Jararaca. ...
For instance, it has been reported that bradykinin is synthesized in skeletal muscle areas during contraction. Because the B2 ... In light of our results, it seems that bradykinin formation during muscle contraction may play an important part in the ... In this experiment, we studied the effect of bradykinin on noradrenaline spillover in the in situ canine gracilis muscle, using ... bradykinin receptor facilitates noradrenaline spillover, it may be involved in the increase associated with contraction. ...
The bradykinin BK2 receptor mediates angiotensin II receptor type 2 stimulated rat duodenal mucosal alkaline secretion.. ... BACKGROUND: This study investigates bradykinin and nitric oxide as potential mediators of AT2-receptor-stimulated duodenal ...
... and enhances the action of bradykinin by inhibiting the peptidases that inactivate it. It acts as an indirect hypotensive agent ... Bradykinin-potentiating peptide 11gAdd BLAST. 11. Amino acid modifications. Feature key. Position(s). DescriptionActions. ... sp,P0DL01,BPPBG_BOTJA Bradykinin-potentiating peptide 11g OS=Bothrops jararaca OX=8724 PE=1 SV=1 QARPRHPKIPP Align. Format. Add ... This peptide both inhibits the activity of the angiotensin-converting enzyme (ACE) and enhances the action of bradykinin by ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Targeted disruption of a B2 bradykinin receptor gene in mice eliminates bradykinin action in smooth muscle and neurons. J Biol ... In vitro, bradykinin treatment either increased or decreased ECM production, depending on the cell type used. Bradykinin ... Although, to our knowledge, nothing is known about the effect of bradykinin on uPA activity, bradykinin was found to be one of ... In vivo bradykinin B2 receptor activation reduces renal fibrosis. Joost P. Schanstra,1 Eric Neau,1 Pascale Drogoz,1 Miguel A. ...
Bradykinin B2 receptor antagonist Total of all reporting groups Arm/Group Description Placebo was normal saline Aminocaproic ... HOE 140 (a bradykinin B2 receptor a... Arm/Group Description: Normal saline (placebo) was started in the operating room after ... HOE 140 (a bradykinin B2 receptor a... Arm/Group Description: Normal saline (placebo) was started in the operating room after ... HOE 140 (a bradykinin B2 receptor a... Arm/Group Description: Normal saline (placebo) was started in the operating room after ...
Rabbit polyclonal Bradykinin antibody conjugated to Biotin. Validated in IP, ELISA, RIA and tested in Human. Immunogen ... Bradykinin is released from kininogen by plasma kallikrein.. Hydroxylation of Pro-383 occurs prior to the release of bradykinin ... For the three of our bradykinin antibodies, ab47864, ab14391and ab47686, the immunogen used was from a.a. 381- 389 of the human ... https://www.abcam.com/Bradykinin-antibody-ab14391.html https://www.abcam.com/Bradykinin-antibody-ab47686.html I hope this ...
... although bradykinin decreases significantly, inferring that bradykinin is critical for protecting the kidney in diabetics. Here ... Genotypes are wild type at both the insulin 2 and the bradykinin B2 loci (WT = Ins2 +/+, Bdkrb2 +/+); wild type for insulin and ... The mice having the null allele for the bradykinin B2 receptor (9) were backcrossed to wild-type C57BL/6J at least six times ... Quantitative RT-PCR. Total RNA was extracted from the whole right kidney of mice, and the mRNA expression of the bradykinin B1 ...
Bradykinin acetate salt for your research needs. Find product specific information including CAS, MSDS, protocols and ... Bradykinin receptor antagonist. Application The Bradkykinin amid peptide des-Arg9-[Leu8]-Bradykini. n is used as a bradykinin-1 ... des-Arg9-[Leu8]-Bradykinin acetate salt ≥97% (HPLC) Synonym: Arg-. Pro-. Pro-. Gly-. Phe-. Ser-. Pro-. Leu ... Bradykinins, Cell Biology, Cell Signaling and Neuroscience, Peptides and Proteins, Peptides for Cell Biology ...
The bradykinin analogue B4146, a competitive antagonist-partial agonist of bradykinin, was used in three groups of normotensive ... The bradykinin antagonist produced an average increase in mean arterial pressure of approximately 13 mm Hg for all groups. In ... Hypertensive effect of a bradykinin antagonist in normotensive rats.. A Benetos, I Gavras, H Gavras ... Since smaller doses of B4146, sufficient to block exogenous bradykinin, do not cause changes in normal blood pressure, we ...
... primarily through the bradykinin receptor 2 pathway. Notably, bradykinin sensitization of TRPV1 in peptidergic nociceptors was ... primarily through the bradykinin receptor 2 pathway. Notably, bradykinin sensitization of TRPV1 in peptidergic nociceptors was ... We found that bradykinin notably enhances the excitability of peptidergic nociceptors, and sensitizes TRPV1, ... We found that bradykinin notably enhances the excitability of peptidergic nociceptors, and sensitizes TRPV1, ...
Browse our Bradykinin RB2/BDKRB2 RNAi catalog backed by our Guarantee+. ... Bradykinin RB2/BDKRB2 RNAi available through Novus Biologicals. ... Bradykinin RB2/BDKRB2 RNAi. We offer Bradykinin RB2/BDKRB2 RNAi ... Alternate Names for Bradykinin RB2/BDKRB2 RNAi. Bradykinin RB2/BDKRB2 RNAi, BDKRB2 RNAi, B2 bradykinin receptor RNAi, B2R RNAi ... Our Bradykinin RB2/BDKRB2 RNAi can be used in a variety of model species: Human. Use the list below to choose the Bradykinin ...
Bradykinin caused platelet adhesion on the apparently unbroken endothelium of the femoral vein, decreased peripheral vascular ...
Browse our Bradykinin RB1/BDKRB1 Lysate catalog backed by our Guarantee+. ... Bradykinin RB1/BDKRB1 Lysates available through Novus Biologicals. ... Alternate Names for Bradykinin RB1/BDKRB1 Lysates. Bradykinin RB1/BDKRB1 lysate, BDKRB1 lysate, B1 bradykinin receptor lysate, ... Our Bradykinin RB1/BDKRB1 Lysates can be used in a variety of model species: Human. Use the list below to choose the Bradykinin ...
Increased circulating bradykinin during hypothermia and cardiopulmonary bypass in children.. L M Pang, S A Stalcup, J S Lipset ... Increased circulating bradykinin during hypothermia and cardiopulmonary bypass in children.. L M Pang, S A Stalcup, J S Lipset ... Increased circulating bradykinin during hypothermia and cardiopulmonary bypass in children.. L M Pang, S A Stalcup, J S Lipset ... Bradykinin was measured by radioimmunoassay in blood samples obtained before, during and after profound hypothermia (to 18 ...
ACE Inhibition and Bradykinin-Mediated Renal Vascular Responses. EDHF Involvement. John D. Imig ...
Bradykinin Fragment 1-8 acetate salt hydrate for your research needs. Find product specific information including CAS, MSDS, ... Bradykinin Fragment 1-8 acetate salt hydrate ≥97% (HPLC) Synonym: [des-Arg9]-Bradykinin acetate salt hydrate ... Bradykinins, Cell Biology, Cell Signaling and Neuroscience, Neuropeptides, Peptides and Proteins, Peptides for Cell Biology ...
  • Together with colleagues Wilson Teixeira Beraldo and Gastão Rosenfeld, they discovered the powerful hypotensive effects of bradykinin in animal preparations. (wikipedia.org)
  • The increased interstitial fibrosis in B2 -/- mice was accompanied by a decreased activity of plasminogen activators (PAs) and metalloproteinase-2 (MMP-2), enzymes involved in ECM degradation, suggesting that the protective effects of bradykinin involve activation of a B2 receptor/PA/MMP-2 cascade. (jci.org)
  • 4. Use according to any one of the preceding claims, characterized in that the bradykinin antagonist is chosen from compounds which interfere with the effects of bradykinin by binding to its receptor (B1 or B2) and preferably to the B2 receptor. (freepatentsonline.com)
  • pain and myocardial reperfusion arrhythmias, bronchial asthma and allergic rhinitis, toxic shock and circulatory collapse, orthostatic hypotension and possibly other B 2 mediated effects of bradykinin that are still ill-defined, such as pain, bowel hypermobility and diarrhea of chronic inflammatory intestinal disease, painful arthritis, neuralgia, etc. (wipo.int)
  • It has not been possible to further evaluate the physiological effects of bradykinin during fetal and newborn life in the mouse or rat due to the limits imposed by size and immaturity. (physiology.org)
  • 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. (aspetjournals.org)
  • The novel peptide bradykinin receptor antagonist, B9340, was used to oppose the effects of bradykinin. (ed.ac.uk)
  • In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. (nel.edu)
  • While mast cell -mediated angioedema can be successfully treated with antihistamines and glucocorticosteroids and with omalizumab as a prophylactic treatment [ 6 ], Bk-AE requires interventions that target the synthesis or receptor activity of bradykinin. (biomedcentral.com)
  • We show here that genetic ablation ( B2 -/- mice) or pharmacological blockade of the bradykinin B2 receptor increases UUO-induced interstitial fibrosis in mice, whereas transgenic rats expressing increased endogenous bradykinin show reduced UUO-induced interstitial fibrosis. (jci.org)
  • Since smaller doses of B4146, sufficient to block exogenous bradykinin, do not cause changes in normal blood pressure, we conclude that endogenous bradykinin does contribute to normal blood pressure maintenance, but its effect can be demonstrated only if very high doses of its antagonist are injected, maybe because a high concentration of the compound is necessary to displace not only circulating but possibly tissue receptor-bound bradykinin as well. (ahajournals.org)
  • In sample of plasma from each patient, concentrations of endogenous bradykinin produced by kinin-forming activitation in plasma during a period of 60 minutes were measured in vitro using a physical chemical technique. (ssc.ca)
  • Bradykinin dilates blood vessels via the release of prostacyclin , nitric oxide , and Endothelium-Derived Hyperpolarizing Factor . (wikipedia.org)
  • BACKGROUND: This study investigates bradykinin and nitric oxide as potential mediators of AT2-receptor-stimulated duodenal mucosal alkaline secretion. (gu.se)
  • We postulate that bradykinin plays a protective role in cardiac anaphylaxis by accumulating at the luminal surface of the coronary endothelium and promoting, in an autocrine mode, a B 2 -receptor-mediated production of nitric oxide and prostacyclin in concentrations sufficient to elicit a paracrine effect on coronary vascular smooth muscle, thus opposing the vasoconstricting effects of other anaphylactic mediators. (ahajournals.org)
  • 13 Because cardiac anaphylaxis is associated with marked ischemia caused by an array of coronary-vasoconstricting agents 1 and ischemia increases bradykinin outflow from the heart, 10 we questioned whether bradykinin production is increased during cardiac anaphylaxis and, if so, whether this nonapeptide may function as a mitigating factor against threatening vasoconstricting mediators. (ahajournals.org)
  • Bradykinin (BK) is a nonapeptide that contributes to inflammatory responses, mediates pain signals and influences blood pressure. (diva-portal.org)
  • Bradykinin is a physiologically and pharmacologically active nonapeptide produced in the body in response to many kinds of injuries. (phdify.com)
  • We offer Bradykinin RB1/BDKRB1 Lysates for use in common research applications: Western Blot. (novusbio.com)
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  • Most of the physiological responses to bradykinin appear to be mediated through activation of the B 2 receptor, which is the most prevalent receptor subtype within the body. (physiology.org)
  • The circulating concentrations of bradykinin increased significantly as body temperature decreased during surface cooling. (ahajournals.org)
  • 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. (ahajournals.org)
  • This is the first in vivo demonstration that hypothermia leads to an increase in the circulating concentrations of bradykinin. (ahajournals.org)
  • Bradykinin is a polypeptide that circulates in the plasma in very low concentrations in comparison with the amount of bradykinin found in various body tissues. (hmdb.ca)
  • Kininogen concentrations in left atrial blood decreased within 1 to 2 minutes after beginning ventilation with O 2 , and free bradykinin was detected in left atrial blood. (ahajournals.org)
  • Study the relationships of the profiles for bradykinin and des-Arg9-bradykinin with gender and the concentrations of angiotensin I-converting enzyme, aminopeptidase P, and carboxypeptidase N. (ssc.ca)
  • We offer Bradykinin RB2/BDKRB2 RNAi for use in common research applications. (novusbio.com)
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  • Our Bradykinin RB2/BDKRB2 RNAi can be used in a variety of model species: Human. (novusbio.com)
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  • The present study showed that bradykinin precursor, kininogen, is present in arterial blood of the fetal lamb by 61 days of gestation and that its concentration increases toward term. (ahajournals.org)
  • Associated with a mean increase in brachial arterial blood Po 2 to 44 mm Hg, a value equivalent to that in the ventilated exteriorized fetus, kininogen concentration fell, and free bradykinin was detected in the brachial arterial blood of 3 of the 6 fetuses. (ahajournals.org)
  • The hypothesis is presented diat bradykinin is produced from kininogen in the lungs of the fetal lamb when oxygenated, and that the maximal rate of production occurs during the first few minutes after expansion of the lungs or exposure of the ewe and fetus to hyperbaric O 2 . (ahajournals.org)
  • The formation of bradykinin in human plasma is basically due to interaction of three proteins (Hageman factor, prekallikrein and high molecular weight kininogen) to anionic surfaces (Figures 1a and 1b). (phdify.com)
  • We found that bradykinin notably enhances the excitability of peptidergic nociceptors, and sensitizes TRPV1, primarily through the bradykinin receptor 2 pathway. (frontiersin.org)
  • We found that bradykinin directly triggered GLUT4myc translocation and increased the rate of glucose uptake in a dose-dependent manner in these cells. (diabetesjournals.org)
  • Hydroxylation of Pro-383 occurs prior to the release of bradykinin. (abcam.com)
  • [2-A few of these reports studied volatile anesthetic effects on the vasomotor actions of bradykinin, serotonin, and other inflammatory mediators. (asahq.org)
  • The data suggest that bradykinin may play a regulatory role in the central control of blood pressure by stimulating sites that are near the dorsal and dorsal lateral surfaces of the medulla and accessible to kinins in cerebrospinal fluid and in the cerebral arterial circulation. (biomedsearch.com)
  • These data strongly suggest that bradykinin, acting via B2R, acts as an important signal directing the invasion of glioma cells toward blood vessels," concluded Montana and Sontheimer in their paper. (oncologynurseadvisor.com)
  • In the present study, we report that cardiac bradykinin production is increased during anaphylaxis and that anaphylactic coronary vasoconstriction and ischemic arrhythmias, which are aggravated by bradykinin B 2 -receptor blockade, are in contrast alleviated by inhibitors of bradykinin breakdown. (ahajournals.org)
  • Using this approach, it was found that some bradykinin analogs are effective inhibitors of bradykinin. (wipo.int)
  • This tPA-triggered generation of bradykinin could participate in the deleterious effects of thrombolysis and is a potential target to improve neurological outcome in tPA-treated patients. (frontiersin.org)
  • Uncontrolled generation of bradykinin, on the other hand, occurs when complement-1 inhibitor (C1-INH) is either deficient or non-functioning. (biomedcentral.com)
  • The physiological role of C1-INH is to control the generation of bradykinin after activation of the contact system. (biomedcentral.com)
  • Effect of histamine and bradykinin on lymph and tissue fluid composition in the rabbit hindlimb: evidence for two compartments in tissue fluid. (biomedsearch.com)
  • In the rabbit hindleg lymph and tissue fluid were collected before and during close intraarterial infusions of histamine (2.5 and 10 micrograms/min) or bradykinin (0.4 microgram/min). (biomedsearch.com)
  • Lymph flow decreased in the controls and it was not significantly influenced by histamine but was in the majority of animals (14 of 20) grossly augmented by bradykinin. (biomedsearch.com)
  • A significant share is mediated by mast-cell mediators such as histamine, but a substantial proportion are unrelated to mast-cell activation and mediated by bradykinin (Bk-AE). (biomedcentral.com)
  • Hypertensive effect of a bradykinin antagonist in normotensive rats. (ahajournals.org)
  • The bradykinin analogue B4146, a competitive antagonist-partial agonist of bradykinin, was used in three groups of normotensive unanesthetized Wistar rats. (ahajournals.org)
  • Bradykinin injected into the fourth cerebral ventricle of unanesthetized rats produced a pressor effect with a shorter latency and a larger maximal effect than when injected in the third or lateral ventricles. (biomedsearch.com)
  • Montana and Sontheimer also learned that bradykinin acts as a chemoattractant, guiding glioma cells toward blood vessels in the brains of rats. (oncologynurseadvisor.com)
  • Results: Bradykinin increased plasma extravasation eight- to ninefold above baseline in both pentobarbital- and isoflurane-anesthetized rats. (asahq.org)
  • Venom Bradykinin-Related Peptides (BRPs) and Its Multiple Biological Roles, An Integrated View of the Molecular Recognition and Toxinology Gandhi Rádis Baptista, IntechOpen, DOI: 10.5772/52872. (intechopen.com)
  • BRADYKININ is a nine-amino acid peptide with a molecular weight of 1.06 kDa. (diff.org)
  • Bradykinin and kallidin (The Kinins) are formed from the high and low molecular weight kininogens, by the action of serine protease kallikreins, both in plasma and peripheral tissues. (phdify.com)
  • Hence, we investigated whether the effect of an ACE inhibitor on the lower limit of CBF autoregulation is mediated by the potentiation of bradykinin-mediated vasodilatation. (ahajournals.org)
  • a non-selective NOS inhibitor), L -canavanine (a specific inhibitor of inducible NOS) or HOE 140 (a bradykinin B 2 receptor antagonist) was administered 45 min before the infusion of glypressin. (clinsci.org)
  • The signalling pathway was confirmed by the use of PD098059 [the inhibitor of MAPK kinase-1 (MEK-1) activation], AACOCF3 (an inhibitor of cPLA2) and indomethacin (an inhibitor of cyclo-oxygenase), which all reduced bradykinin-stimulated cAMP synthesis. (strath.ac.uk)
  • Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1st bolus of Gd-DTPA over the first hour, and then re-imaged with a 2nd bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. (biomedcentral.com)
  • Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway. (diabetesjournals.org)
  • Intracellular INK pathway and TNF-alpha might provide key links between inflammatory mediators like IL-1 beta and airway hyperresponsiveness to bradykinin. (lu.se)
  • To evaluate the hypothesis that sphingosine-1-phosphate (S1P) and cAMP attenuate increased permeability of individually perfused mesenteric microvessels through a common Rac1-dependent pathway, we measured the attenuation of the peak hydraulic conductivity (L p ) in response to the inflammatory agent bradykinin (BK) by either S1P or cAMP. (elsevier.com)
  • Figures 1a and 1b show the tissue and plasma biosynthetic pathway of bradykinin. (phdify.com)
  • We describe the effects in isolated model sensory neurons of LAs on responses to the algogenic and sensitizing peptide, bradykinin (BK). (ovid.com)
  • ACE is critical in the degradation of bradykinin, which is hypothesized to accumulate excessively in some patients taking ACEI for their hypertension. (biomedcentral.com)
  • Bradykinin raises internal calcium levels in neocortical astrocytes causing them to release glutamate , though this finding has only been confirmed in-vitro. (wikipedia.org)
  • Bradykinin is a physiologically and pharmacologically active peptide of the kinin group of proteins , consisting of nine amino acids . (wikipedia.org)
  • These analogs generally have modifications or additions to one or more of the nine bradykinin amino acids. (wipo.int)