Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.01 seconds)

Angiotensin-converting enzyme has been solubilized from a particulate fraction of rabbit lung and purified to apparent homogeneity in 11% yield by a procedure including fractionation with DEAE-cellulose and calcium phosphate gel, elution from Sephadex G-200, and lectin affinity chromatography. The molecular weight estimated by equilibrium sedimentation was approximately 129,000, either in the absence or presence of 6 M guanidine hydrochloride. A slightly higher value of 140,000 determined for the reduced, denatured protein by gel electrophoresis in the presence of sodium dodecyl sulfate and a much higher figure derived from gel filtration are probably due to the glycoprotein nature of the enzyme. Its oligosaccharide content accounted for 26% of the weight calculated from its amino acid and carbohydrate composition. The estimated content of sugar residues per mole was: galactose, 57; N-acetylglucosamine, 53; mannose, 43; N-acetylneuraminic acid, 19; and fucose, 4. Threonine and alanine were identified, respectively, as NH2-terminal and COOH-terminal residues by the dansylation procedure and by digestion with carboxypeptidase A. The enzyme was found to contain approximately 1 g atom of zinc per mol. Km values for hydrolysis of hippurylhistidylleucine and angiotensin I were 2.3 and 0.07 mM, and the corresponding turnover numbers were 15,430 and 792 mol/min/mol at 37 degrees. Bradykinin was also a substrate, and release of its COOH-terminal dipeptide, Phe-Arg, was catalyzed at a comparable rate to that of His-Leu from the COOH terminus of angiotensin I. Enzyme activity required the presence of chloride ions and was inhibited by EDTA and by low concentrations of Bothrops bradykinin-potentiating peptides. In addition, hydrolysis of hippurylhistidylleucine was inhibited competitively by other defined peptides, including di- and tripeptides, which were not substrates.
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PMID:Pulmonary angiotensin-converting enzyme. Structural and catalytic properties. 16 57

Bradykinin and a range of peptide analogues induced a dose-dependent release of histamine from rat peritoneal mast cells. The characteristics of the release were not consistent with the involvement of defined bradykinin receptors but indicated that the peptide acted through the putative mast cell polyamine receptor. Consistently, the effect of bradykinin was largely confined to serosal mast cells of the rat and hamster, while human histaminocytes were essentially unresponsive. These data do then not support a general role for kinin-induced activation of mast cells in human allergic disease.
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PMID:Histamine secretion from mast cells stimulated with bradykinin. 169 64

The effect of a variety of non IgE-mediated stimuli on histamine release from mast cells from different locations is described. Sensory neuropeptides are shown to resemble other polycationic compounds in preferentially activating mast cells from the rat while having a limited effect on human mast cells, except possibly those from skin. Similar results were obtained with the putative non-adrenergic, non-cholinergic neurotransmitter ATP, thereby questioning the role of neuronal mast cell activation in allergy and inflammation. Bradykinin also acted selectively against rat cells while complement-derived and formylmethionyl peptides were effective against human basophils and cutaneous mast cells. The latter results may indicate a role for the skin cell in local inflammatory responses involving complement activation and in host resistance to bacterial infection. Rat mast cells and human basophils were most responsive to hyperosmolar challenge but significant effects were obtained from human pulmonary mast cells obtained by bronchoalveolar lavage. The latter cells may thus be implicated in exercise-induced asthma. The plasma substitute dextran was a specific secretagogue for the rat while morphine sulphate largely induced histamine release from human cutaneous mast cells. The latter result may account for anaphylactoid reactions to the opiate. In total these data emphasize the functional heterogeneity of mast cells from different locations and highlight the particular pharmacological properties of the skin mast cell in man.
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PMID:Non-IgE-mediated mast cell stimulation. 251 51

Acetylshikonin, a naphthoquinone isolated from the Chinese herb medicine, tzu ts'ao, was demonstrated to inhibit the polymyxin B-induced hind-paw edema in normal as well as in adrenalectomized mice. Liver glycogen content was increased in adrenalectomized mice pretreated with dexamethasone, but not with acetylshikonin. Like diphenhydramine, methysergide and isoproterenol, acetylshikonin reduced the plasma exudation evoked in dorsal hind-paw skin by antidromic stimulation of the saphenous nerve, and in passive cutaneous anaphylactic reaction, bradykinin-, substance P-, compound 48/80-, histamine- and serotonin-induced ear edema. Indomethacin was ineffective in these respects. Bradykinin- and substance P-induced plasma exudation were also significantly reduced when [Thi5,8,D-Phe7]bradykinin and [D-Pro2,D-Trp7,9]substance P were coinjected with bradykinin and substance P, respectively. In isolated rat peritoneal mast cell preparation, acetylshikonin produced a concentration-dependent inhibition of histamine and beta-glucuronidase release from mast cells challenged by compound 48/80. In compound 48/80-pretreated mice, acetylshikonin and isoproterenol produced significantly more inhibitory effect on bradykinin- and substance P-induced plasma exudation than did diphenhydramine in combination with methysergide. Pretreatment with diphenhydramine/methysergide in compound 48/80-pretreated mice significantly further reduced the bradykinin- and substance P-induced plasma exudation if [Thi5,8,D-Phe7]bradykinin and [D-Pro2,D-Trp7,9]substance P were coinjected with bradykinin or substance P, respectively. The results suggest that the inhibitory effect of acetylshikonin on the edematous response is due neither to the release of steroid hormones from the adrenal gland nor to the glucocorticoid activity, but probably partly to the suppression of mast cell degranulation and partly to protection of the vasculature from mediator challenge.
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PMID:Inhibition of hind-paw edema and cutaneous vascular plasma extravasation in mice by acetylshikonin. 753 60

Tryptase is a trypsin-type serine protease that is released from mast cells. Bradykinin (BK) is released directly from kininogens or through activation of either Hageman factor or subsequent plasma prekallikrein. Its nasal administration or inhalation induces allergy-like symptoms. Although elevated levels of tryptase and BK in allergic fluids have been detected, the role of this proteinase and the mechanism of BK production at allergic reaction sites are still unknown. To investigate the pathologic functions of tryptase, the enzyme, purified from human lung, was incubated with normal human plasma, deficient plasmas, kininogens, or prekallikrein. High molecular weight kininogen was then added, and the mixtures were examined for vascular permeability enhancement (VPE) activity, a representative function of bradykinin, using guinea pig skin. Tryptase-treated plasma induced VPE in a dose-dependent manner; activity was lost in the absence of a kininase inhibitor but not an antihistamine drug. Tryptase produced VPE activity from normal or Hageman factor-deficient plasma, but only 30% of this activity was produced from prekallikrein-deficient plasma. Significantly, no activity was obtained from kininogen-deficient plasma. Deficient plasma that were reconstituted with each missing factor resulted in VPE-inducing capacity by tryptase, equivalent to that found with normal plasma. Incubation of tryptase with high or low molecular weight kininogen induced VPE activity in a dose- and incubation time-dependent manner. Prekallikrein incubated with tryptase also generated a soybean trypsin inhibitor-sensitive VPE-inducing activity from high molecular weight kininogen. The loss of tryptase VPE-producing activity as a function of incubation time was found to be a result of spontaneous inactivation of the enzyme and not of the degradation of high molecular weight kininogen by the enzyme. We conclude that tryptase induces VPE by releasing BK, primarily through prekallikrein activation, but also through direct release from kininogens. This indicates that this mast cell-derived proteinase contributes to kinin production in allergic diseases.
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PMID:Induction of vascular permeability enhancement by human tryptase: dependence on activation of prekallikrein and direct release of bradykinin from kininogens. 864 82

We investigated the role of activation of bradykinin receptors and mast cells in the microvascular leakage of the vessels of the skin induced by the intracutaneous (i.c.) injection of bradykinin in the rat. We evaluated the effects of HOE140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a bradykinin B2 receptor antagonist, and ketotifen (4-(1-methyl-4-piperidylidene)4H-benzo[4,5]cyclohepta[1, 2-b]thiophen-10(9H)-one hydrogen fumarate), a histamine H1 receptor antagonist with mast cell stabilizing properties, on the skin response. Evans blue dye extravasation served as an index of the increase in vascular permeability. Bradykinin (2-100 nmol/site i.c.) induced the extravasation of Evans blue dye in a dose-dependent manner. Ketotifen (20 mg/kg i.p.) significantly inhibited the leakage of dye induced by bradykinin (10 nmol/site i.c.) by 66.2%, while HOE140 (1 mg/kg i.v.) had no effect. The concomitant injection of HOE140 (0.2, 2 nmol/site) and bradykinin (10 nmol/site i.c.), also did not significantly reduce the extravasation of dye. We conclude that the extravasation of plasma induced by the i.c. injection of bradykinin is mediated mainly by stimulation of the skin mast cells, but not by bradykinin B2 receptors.
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PMID:Role of bradykinin B2 receptors and mast cells in the bradykinin-induced skin response in the rat. 886 2

We sought to establish and immunocytochemically characterize primary cultures of human conjunctival epithelial (HCE) cells, and to determine the types of receptors coupled to adenylate cyclase (AC) and phospholipase C (PLC) present on them which may be stimulated following allergic or inflammatory provocation of the tissue. HCE cells possessed the key epithelial cell surface cytokeratins AE1, AE3 and AE5. Signal transduction studies (n > or = 3), using agonists and antagonists, revealed the presence of beta 2-adrenergic (isoproterenol EC50 = 5.2 nM), prostaglandin E2 (EC50 = 168 nM) and vasoactive intestinal peptide (EC50 = 0.69 nM) receptors positively coupled to AC in HCE cells. Bradykinin (EC50 = 0.83 nM), platelet activating factor (EC50 = 4.5 nM), leukotriene C4 (EC50 = 300 nM) and histamine1 (EC50 = 3.1 microM) receptors were coupled to PLC (n = 3 for each). These data suggest that HCE cells in vivo may represent target cells for mast cell mediators and certain neurotransmitters which are released into the tear-film upon allergic provocation of the conjunctiva.
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PMID:Pharmacological analysis of mast cell mediator and neurotransmitter receptors coupled to adenylate cyclase and phospholipase C on immunocytochemically-defined human conjunctival epithelial cells. 926 68

1. Bradykinin is suggested to play a role in the pathophysiology of several acute and chronic diseases, including allergic disorders such as asthma. In the present study, we have investigated the importance of bradykinin in mediating allergic inflammation in rats. 2. To this end we have tested the effects of the B2 receptor antagonists Hoe 140, FR173657 or FR172357 on the pleural inflammatory response triggered by intrapleural (i.pl.) injection of allergen (ovalbumin, 12 microg cavity(-1)) in 14 day-actively sensitized Wistar rats. Analysis of the pleural fluid effluent revealed a sequence of mast cell-dependent inflammatory events, including early protein exudation and neutrophilia and late pleural eosinophil influx. 3. Local treatment with Hoe 140 (0.1 and 1 microg cavity(-1)), FR173657 (1 and 10 microg cavity(-1)) or FR172357 (1 and 10 microg cavity(-1)) inhibited dose-dependently allergen-induced mast cell activation with impairment of pleural plasma leakage, neutrophil accumulation and late eosinophil influx. 4. Moreover, the B2 receptor antagonists also dose-dependently inhibited the allergic like inflammatory pleurisy triggered by bradykinin (50 microg cavity(-1)), which is characterized by acute mast cell degranulation, protein leakage and pleural eosinophil infiltration. 5. Taken together, our findings provide substantial evidence to suggest that bradykinin acting on its B2 receptors play a critical role in mediating allergic mast cell-dependent inflammation in rats, and suggest that B2 receptor antagonists may be useful therapeutically to control allergic dysfunction.
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PMID:Suppressive effect of distinct bradykinin B2 receptor antagonist on allergen-evoked exudation and leukocyte infiltration in sensitized rats. 1038 28

Intravital microscopic techniques were used to examine the mechanisms underlying bradykinin-induced leukocyte/endothelial cell adhesive interactions (LECA) and venular protein leakage (VPL) in single postcapillary venules of the rat mesentery. The effects of bradykinin superfusion to increase LECA and VPL were prevented by coincident topical application of either a bradykinin-B(2) receptor antagonist, a cell-permeant superoxide dismutase (SOD) mimetic or antioxidant, or inhibitors of cytochrome P-450 epoxygenase (CYPE) or protein kinase C (PKC) but not by concomitant treatment with either SOD, a mast cell stabilizer, or inhibitors of nitric oxide synthase, cyclooxygenase, xanthine oxidase, NADPH oxidase, or platelet-activating factor. Immunoneutralizing P-selectin or intercellular adhesion molecule-1 (ICAM-1) completely prevented bradykinin-induced leukocyte adhesion and emigration but did not affect VPL. On the other hand, stabilization of F-actin with phalloidin prevented bradykinin-induced leukocyte emigration and VPL but did not alter leukocyte adhesion. These data indicate that bradykinin induces LECA in rat mesenteric venules via a B(2)-receptor-initiated, CYPE-, oxidant- and PKC-mediated, P-selectin- and ICAM-1-dependent mechanism. Bradykinin also produced VPL, an effect that was initiated by stimulation of B(2) receptors and involved CYPE and PKC activation, oxidant generation, and cytoskeletal reorganization but was independent of leukocyte adherence and emigration.
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PMID:Bradykinin-induced proinflammatory signaling mechanisms. 1238 46

Protective vasodilation in response to tissue injury and acid back diffusion is associated with release of bradykinin in the rat stomach. We hypothesized that bradykinin might be involved in mechanisms behind such vasodilation via influence on mast cells and sensory neurons. Acid back diffusion after mucosal barrier disruption with hypertonic saline evoked degranulation of mast cells in the rat stomach wall. Acid back diffusion was also associated with increased luminal release of histamine and gastric blood flow in normal rats, but not in mast cell-deficient rats. Bradykinin (BK(2)) receptor blockade inhibited degranulation of submucosal mast cells in the stomach and attenuated gastric vasodilation both in response to acid back diffusion and after stimulation of sensory neurons with capsaicin. Gastric vasodilation caused by mucosal injury with hypertonic saline alone was associated with degranulation of mucosal mast cells. These events were unaffected by inhibition of prostaglandin synthesis, whereas bradykinin (BK(2)) receptor blockade was associated with abolished vasodilation and inhibition of mucosal mast cell degranulation. We conclude that bradykinin is involved in gastric vasodilation caused by hypertonic injury alone via influence on mast cells, and by acid back diffusion via influence on both sensory neurons and mast cells.
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PMID:Role of bradykinin in gastric vasodilation caused by hypertonic saline and acid back diffusion. 1509 8


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