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  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Leukotrienes (C4, D4) have been shown to enhance mucus seeretion in both isolated human airway tissue and intact canine tracheain vivo. They also have been implicated as putative mediators in several airways diseases. In previous canine studies the mucus enhancing effect of leukotriene-C4 was blocked by atropine, FLP 55,712, and hexamethonium but not by cutting the superior laryngeal and vagus nerves. We anesthetized mongrel dogs with chloralose (100 mg/kg) and urethane (500 mg/kg) and ventilated them on a pump. To visualize the secretions from submucosal glands, we exposed the mucosa of the upper trachea and coated its surface with powdered tantalum. Seeretions from the glands formed elevation in the tantalum layer (hillocks) with time: the number of tracheal hillocks (an index of mucus secretion) was measured at one or more of the four time points on six dogs after each treatment of the treatment sequence: no LTC4, LTC4, no LTC4+ blocker, and LTC4+ blocker. The potential blocker was diphenhydramine, an H1 antagonist for histamine. LTC4 was injected into the cranial thyroid artery which directly feeds the tracheal segment. We observed hillocks through a dissecting microscope, and the number of hillocks per 1.2 cm2 were counted for a 1–4 min interval. In 6 dogs with 12 responses, LTC4 (10 μg) gave a positive response that was significantly different from control (p〈0.01–0.05) at 2–4 min. Diphenhydramine (n=6), 0.5 mg/kg, a dose which blocked a histamine challenge without blocking an acetylcholine challenge of secretion, gave a statistically significant (p〈0.01–0.05) reduction in mucus secretion at 1–4 min. These results support the conclusion that leukotriene C4 induces mucus secretion in dogs that is blocked by prior diphenhydramine administration. This would indicate histamine has a role, but as yet an unknown mechanism in the action of leukotriene-C4 in enhancing mucus.
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  • 2
    ISSN: 1420-908X
    Keywords: Key words: Bradykinin — Kinin receptors — Intracellular Ca2+— Epithelial cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective: To determine which types of kinin receptor are present in human bronchial epithelial cells we studied the capability of bradykinin to mobilize intracellular Ca2+ ([Ca2+] i) in a human bronchial epithelial cell line (16HBE cells).¶Material: Human bronchial epithelial cell line transformed with an original defective simian virus 40 (SV40).¶Treatment: Bradykinin (0.1 pM to 0.1 μM), des-Arg9 bradykinin (1 μM), des-Arg10 kallidin (1 μM), indomethacin (1 μM), phosphoramidon (1 μM), captopril (1 μM), des-Arg9-[Leu8]bradykinin (1 μM), HOE 140 (DArg-[Hyp3, Thi5, DTic7, Oic8]-bradykinin) (1 μM), and NPC 16731 (DArg-[Hyp3, Thi5, DTic7, Tic8]-bradykinin) (1 μM).¶Methods: The mobilization of [Ca2+]i was determined by the fura-2 method. Two sample Wilcoxon rank-sum (Mann-Whitney) test was used for statistical calculations.¶Results: Bradykinin, but not the selective agonists for kinin B1 receptor des-Arg9 bradykinin and des-Arg10 kallidin, increased the mobilization of [Ca2+]i (EC50, 0.079 ± 0.009 nM) in 16HBE cells in a concentration-dependent manner. Pretreatment with the cyclooxygenase inhibitor indomethacin (1 μM) or the peptidase inhibitors, phosphoramidon (1 μM) or captopril (1 μM), did not affect the response to bradykinin. The kinin B1 receptor antagonist, des-Arg9-[Leu8]bradykinin (1 μM), was inactive. HOE 140 and NPC 16731, two selective antagonists of the kinin B2 receptor abolished the response to bradykinin (IC50 of HOE 140 and NPC 16731 were 0.52 ± 0.037 nM and 1.67 ± 0.41 nM, respectively).¶Conclusions: The present data indicate the presence of kinin B2 receptors in the 16HBE cells.
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  • 3
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Leukotriene B4 (LTB4), an inflammatory mediator, is a potent chemoattractant for neutrophils that plays an important role in nasal secretion via release of elastase. Nitric oxide (NO) is an important modulator of leucocyte–endothelial cell interactions, endogenously produced in large quantities in the paranasal sinuses.To examine the role of NO in LTB4-stimulated nasal secretion.A newly-developed method for isolating and superfusing a nasal segment in dogs was used.Instillation of LTB4 into the nasal segment caused a time-dependent increase in the volume of airway fluid and in the recruitment of neutrophils. N(G)-nitro-l-arginine-methylester (L-NAME), an inhibitor of NO synthase, prevented LTB4-induced neutrophil recruitment and nasal secretion.These studies show that NO modulates LTB4-induced neutrophil recruitment and subsequent fluid secretion in the nose, and they suggest a therapeutic role for NO inhibitors in modulating neutrophil-dependent nasal secretion.
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  • 6
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Methods and Results A method for isolating and superfusing a segment of the nasal cavity in the anaesthetized dog was developed. Introduction of Pseudomonas aeruginosa supernatant (PA), which is known to induce IL-8 release, resulted in a marked time-dependent exponential increase in neutrophil recruitment to the nasal chamber. When oxymetazoline (final concentration. 10-5 M), was added to the superfusate, the PA induced-neutrophil migration was inhibited; the addition of benzalchoniul chloride to the superfusate had no effect on the PA induced-neutrophil migration.Conclusion We conclude that a α2 adrenoceptor agonist profoundly inhibits neutrophil migration in response to bacterial products. Our novel method allows continuous introduction of stimuli and monitoring of responses in the nasal mucosa.
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  • 7
    ISSN: 1432-0878
    Keywords: Lysozyme ; Trachea ; Serous cell ; Bethanechol ; Phenylephrine ; Terbutaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Lysozyme is a bacteriolytic enzyme found in respiratory tract fluid. In this study, immunocytochemistry was used to determine the cells of origin of tracheal lysozyme in the ferret. Lysozyme was found in secretory granules of serous but not mucous cells in the submucosal glands, and was absent from the surface epithelium, cartilage, and connective tissue. The exclusive presence of lysozyme in serous gland cells renders it useful as a biochemical marker of that cell type. Measurements of lysozyme assayed from the incubating medium indicated that bethanechol stimulated lysozyme release by 260±80.9% (mean ±SE), phenylephrine by 80±16.4%, and terbutaline by 25±10.2%. Electron-microscopic and immunocytochemical analysis of incubated tissues revealed loss of serous granules and lysozyme immuno-reactivity in response to the drugs. Atropine, propranolol, and phentolamine blocked the stimulatory effects of bethanechol, terbutaline, and phenylephrine, respectively. These findings establish the usefulness of lysozyme as a serous-cell marker and demonstrate that secretory responses of different magnitude are evoked by equimolar concentrations of alpha- and beta-adrenergic and cholinergic drugs.
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  • 8
    ISSN: 1432-0878
    Keywords: Trachea ; Phenylephrine ; Terbutaline ; Methacholine ; Airway mucus secretion ; Serous cell ; Gland morphology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A morphometric analysis was made of alterations in serous cell structure induced by adrenergic and cholinergic agonists. Ferret tracheal rings were exposed for 30 min in vitro to one of the following agonists: phenylephrine, terbutaline, or methacholine (all at 10−5 M). Controls were incubated similarly in medium containing no drugs or medium containing both the agonist and an excess of the appropriate antagonist (phentolamine, propranolol or atropine, all at 10−4 M). Electron microscopic observation and stereological analysis of the incubated samples revealed that the volume density of serous cell granules in controls (0.30 ± 0.02, mean ± SE, n = 4) was significantly reduced by phenylephrine (0.19 ± 0.03, n = 4) and methacholine (0.17 ± 0.01, n = 4), but not by terbutaline (0.27 ± 0.04, n = 4). The presence of antagonists in the medium prevented the observed changes (phenylephrine/phentolamine: 0.29 ± 0.03, n = 3 and methacholine/atropine: 0.33 ± 0.06, n = 3). In addition, the volume density of intracellular vacuoles in controls (0.02 ± 0.005, n = 4) was increased in response to methacholine stimulation (0.12 + 0.05, n = 4), but not in response to the other agonists. This effect was blocked by atropine (0.01 ± 0.00, n = 3). We conclude that serous-cell granules are discharged by both alpha-adrenergic and cholinergic, but not beta-adrenergic stimulation. In addition, cholinergic stimulation evokes the formation of intracellular vacuoles, a possible indication of active ion and water transport.
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  • 9
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Medicine 35 (1984), S. 451-467 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 41 (1979), S. 369-381 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Type of Medium: Electronic Resource
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