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• W2050445045 abstract "1. The long-acting beta(2)-adrenoceptor agonist formoterol (10(-10)-10(-6) m) inhibited the IgE-dependent release of histamine from human lung mast cells in a concentration-dependent manner. Formoterol was more potent and a full agonist relative to the nonselective beta-adrenoceptor agonist isoprenaline. By contrast, the long-acting beta(2)-adrenoceptor agonist salmeterol (10(-10)-10(-6) m) was about two-thirds less efficacious than either formoterol or isoprenaline as an inhibitor of histamine release. 2. Isoprenaline, formoterol and salmeterol (all at 10(-5) m) increased total cell cAMP levels in mast cells over basal by 361+/-90 (P<0.05), 321+/-89 (P<0.05) and 64+/-24% (P>0.05), respectively. 3. Long-term (24 h) incubation of mast cells with formoterol (10(-6) m) or salmeterol (10(-6) m) essentially abolished the subsequent ability of isoprenaline to inhibit histamine release. Both formoterol and salmeterol were more effective at inducing the functional desensitisation than isoprenaline (10(-6) m) or the short-acting beta(2)-adrenoceptor agonist salbutamol (10(-6) m). 4. The desensitisation induced by long-term treatments with salmeterol and formoterol was specific for beta(2)-adrenoceptor-mediated inhibition of histamine release as the inhibitory effects of alternative cAMP-elevating compounds, prostaglandin E(2), a receptor-mediated activator of adenylate cyclase, and forskolin, a direct activator of adenylate cyclase, were unaffected by desensitising treatments. 5. Radioligand binding studies were performed to determine beta(2)-adrenoceptor density in cell membranes after pretreatment (24 h) of cells with agonists. Isoprenaline, formoterol and salmeterol (all at 10(-6) m) reduced beta(2)-adrenoceptor density by 13+/-5 (P>0.05), 49+/-13 (P<0.05) and 35+/-17% (P>0.05), respectively. 6. These data indicate that long-term exposure of mast cells to both salmeterol and formoterol can cause substantial levels of desensitisation to beta(2)-adrenoceptor-mediated responses in mast cells." @default.
• W2050445045 created "2016-06-24" @default.
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• W2050445045 date "2004-01-01" @default.
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• W2050445045 title "Desensitisation of mast cell<i>β</i>₂-adrenoceptor-mediated responses by salmeterol and formoterol" @default.
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• W2050445045 doi "https://doi.org/10.1038/sj.bjp.0705599" @default.
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