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Airway Smooth Muscle Contraction (airway + smooth_muscle_contraction)
Selected AbstractsSelegiline, an MAO-B inhibitor, attenuates airway smooth muscle contraction in the rat tracheaJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2004Maki Yoshimura Selegiline is widely used for Parkinson's disease and sometimes for Alzheimer's disease. It is reported to affect intracellular Ca2+ concentration. Since intracellular Ca2+ is partly regulated by phosphatidylinositol (PI) response and is important for smooth muscle contraction, selegiline may affect airway smooth muscle tension. We examined the effects of selegiline on acetylcholine (ACh)- and KCl-induced contractile and PI responses in rat trachea. The trachea was cut into 3-mm-wide ring segments or 1-mm-wide slices. ACh (3 ,M, 50% effective dose) or KCl (40mM) was added, and ring relaxation was induced by the addition of selegiline. Tracheal slices were incubated with [3H]myo -inositol and 3 ,M ACh in the presence of selegiline, and [3H]inositol monophosphate (IP1) was measured. Selegiline dose-dependently attenuated ACh- and KCl-induced tracheal ring contractions. Fifty-percent inhibitory doses (ID50) of selegiline against ACh- and KCl-induced contraction were 120±30 ,M and 80±20 ,M, respectively. Basal and ACh-induced IP1 accumulation were 2.20±0.20 Bq and 7.88±0.23 Bq, respectively, and selegiline at a dose of 1000 ,M attenuated ACh-induced IP1 accumulation (5.44±0.30 Bq). These results suggest that selegiline inhibits contractile responses through the inhibition of voltage-operated Ca2+ channels and the PI response. [source] Cigarette smoke suppresses in vitro allergic activation of mouse mast cellsCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2009E. Mortaz Summary Background Mast cells are important effector cells in innate or acquired immunity that contribute to host defence. Excessive activation of mast cells can result in the development of allergic diseases, including atopic asthma. Mast cell activation by IgE and specific antigen induces the cells to release spasmogenic, vasoactive and pro-inflammatory mediators, which enhance airway smooth muscle contraction, vascular permeability and inflammatory cell recruitment. Recently, we have demonstrated that exposure of mast cells to cigarette smoke medium (CSM) triggered mast cells to produce chemokines. On the other hand, smoking may decrease the risk of allergic sensitization, which could be explained by a reduced IgE production or a diminished response of mast cells to activation of the IgE receptor. Objective In this study, we investigated the effect of CSM on the allergic activation of mast cells through IgE and antigen. Methods Primary cultured murine mast cells were exposed to CSM and activated with IgE and antigen or lipopolysaccharide (LPS). The release of granules, production of leukotrienes, chemokines and cytokines was determined in the supernatants by ELISA. The effect of CSM exposure on intracellular signalling, especially the nuclear factor (NF)-,B and extracellular signal-regulated kinase (Erk)1/2 pathways, was analysed by Western blotting. Results CSM suppressed IgE-mediated degranulation and cytokine release, but no effect was observed on leukotriene release. CSM induced phosphorylation of Erk1/2 in mast cells. In CSM-exposed mast cells, activating transcription factor (ATF)-1 was phosphorylated after stimulation with IgE/Ag. LPS-activated mast cells were not influenced by CSM. Conclusion Our study suggests that exposure to cigarette smoke may lead to a reduced allergic activation of mast cells without affecting their response to activation via e.g. bacterial-derived LPS. [source] Role of Ca2+ mobilization and Ca2+ sensitization in 8-iso-PGF2, -induced contraction in airway smooth muscleCLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2009A. Shiraki Summary Background Isoprostanes are prostaglandin (PG)-like compounds synthesized by oxidative stress, not by cyclooxygenase, and increase in bronchoalveolar lavage fluid of patients with asthma. The airway inflammation implicated in this disease may be amplified by oxidants. Although isoprostanes are useful biomarkers for oxidative stress, the action of these agents on airways has not been fully elucidated. Objective This study was designed to determine the intracellular mechanisms underlying the effects of oxidative stress on airway smooth muscle, focused on Ca2+ signalling pathways involved in the effect of 8-iso-PGF2,. Methods Using simultaneous recording of isometric tension and F340/F380 (an indicator of intracellular concentrations of Ca2+, [Ca2+]i), we examined the correlation between tension and [Ca2+]i in response to 8-iso-PGF2, in the fura-2 loaded tracheal smooth muscle. Results Augmented tension and F340/F380 by 8-iso-PGF2, were attenuated by ICI-192605, an antagonist of thromboxane A2 receptors (TP receptors). Moreover, D609, an antagonist of phosphatidylcholine-specific phospholipase C, markedly reduced both the tension and F340/F380 induced by 8-iso-PGF2,, whereas U73122, an antagonist of phosphatidylinositol-specific phospholipase C, modestly inhibited them by 8-iso-PGF2,. SKF96365, a non-selective antagonist of Ca2+ channels, markedly reduced both tension and F340/F380 by 8-iso-PGF2,. However, diltiazem and verapamil, voltage-dependent Ca2+ channel inhibitors, modestly attenuated tension although their reduction of F340/F380 was not different from that by SKF96365. Y-27632, an inhibitor of Rho-kinase, significantly attenuated contraction induced by 8-iso-PGF2, without reducing F340/F380, whereas GF109203X and Go6983, protein kinase C inhibitors, did not markedly antagonize them although reducing F340/F380 with a potency similar to Y-27632. Conclusion 8-iso-PGF2, causes airway smooth muscle contraction via activation of TP receptors. Ca2+ mobilization by SKF96365- and D609-sensitive Ca2+ influx and Ca2+ sensitization by Rho-kinase contribute to the intracellular mechanisms underlying the action of 8-iso-PGF2,. Rho-kinase may be a therapeutic target for the physiologic abnormalities induced by oxidative stress in airways. [source] s -CARBOXYMETHYLCYSTEINE INHIBITS CARBACHOL-INDUCED CONSTRICTION OF EPITHELIUM-DENUDED RAT AND HUMAN AIRWAY PREPARATIONSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2008Dragan Pavlovic SUMMARY 1The effects of s-carboxymethyl-l-cysteine (S-CMC), either administered orally to rats or incubated with tissue preparations from rats and humans, on isometric contractions of tracheal smooth muscle were investigated in the present study using an improved in vitro model of tracheal tube or ring preparations. The involvement of the tracheal epithelium in the observed effects was also investigated. 2The experimental model permitted selective perfusion of the airway tube, luminal-IN or serosal,OUT, and measurement of airway smooth muscle contraction or relaxation in preparations with (+) or without (,) epithelium (Ep), excluding direct effects of airway mucus. 3We found that oral pretreatment of rats with S-CMC (mixed with water; 200 mg/kg per day for 2 weeks), but not short pre-incubation of preparations in vitro (10,3 mol/L S-CMC for 1 h), diminished the sensitivity of ,Ep preparations to carbachol compared with controls (EC50 (,log10 mol/L) values: 5.5 ± 0.1 vs 5.8 ± 0.1, respectively, for IN perfusion (P < 0.005); 5.6 ± 0.1 vs 5.9 ± 0.1, respectively, for OUT perfusion (P < 0.005)), whereas the sensitivity of preparations to aminophylline was not affected. Normal sensitivity to carbachol stimulation was re-established if preparations were pre-incubated with capsaicin. 4It was also found that longer pre-incubation (4 h) of ring-preparations of human bronchus with S-CMC (10,5 mol/L) in vitro resulted in a diminished response to carbachol stimulation. 5In conclusion, S-CMC had small inhibitory effects on the sensitivity of rat and human airway smooth muscle to carbachol, particularly in endothelium-denuded preparations. Whether the epithelium was responding to S-CMC by producing some contracting factor(s) requires further investigation. [source] | ||||||||||