Allergen-induced glycoconjugate secretion in guinea-pig trachea in vivo: modulation by indomethacin, BW B70C and ZD-2138.
A method has been established for measurement of tracheal secretions in anaesthetized, ventilated guinea-pigs. The upper trachea was cannulated and perfused with saline. The perfusate was analysed for protein using the Lowry assay and for glycoconjugates ('mucus') by a procedure generating a fluorophore from fucose moieties in the sample. Intravenously infused acetylcholine (ACh) stimulated an increase in glycoconjugate secretion which was maximal after 75 min of ACh administration. Total protein concentration was not increased. Intravenously infused 15-HETE produced a similar increase in glycoconjugate secretion also without increasing protein concentration, but the time of maximal effect was earlier (30 min) than with ACh. Intravenous infusion of allergen (ovalbumin) in antihistamine pretreated, sensitized animals induced a dose-related glycoconjugate secretion which was maximal at 30 min after challenge. Indomethacin potentiated allergen-induced glycoconjugate secretion. The reportedly specific inhibitor of 5-lipoxygenase, ZD-2138, substantially inhibited allergen-induced pulmonary bronchoconstriction but did not influence glycoconjugate secretion. In contrast, the selective 5-, 15-lipoxygenase inhibitor BW B70C significantly attenuated both allergic airway closure and glycoconjugate secretion. These studies demonstrate the practicability of measuring glycoconjugate secretion in guinea-pig trachea in vivo, and that ACh and 15-HETE are potent secretagogues in this species. Further, they suggest that allergic glycoconjugate secretion is mediated, at least in part, via the release of lipid mediators from pathways other than via 5-lipoxygenase.
Department of Pharmacology, Wellcome Foundation Limited, Beckenham, Kent, UK.
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Yeadon
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Price
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Payne
D000109:Acetylcholine / Q000494:pharmacology; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D006001:Glycoconjugates / Q000378:metabolism*; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D006898:Hydroxylamines / Q000494:pharmacology*; D006918:Hydroxyurea / Q000031:analogs & derivatives*; D007213:Indomethacin / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D008782:Methylurea Compounds / Q000494:pharmacology*; D011714:Pyrans / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D000485:Allergens; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006001:Glycoconjugates; D006893:Hydroxyeicosatetraenoic Acids; D006898:Hydroxylamines; D016859:Lipoxygenase Inhibitors; D008782:Methylurea Compounds; D011714:Pyrans; D015363:Quinolones; C080871:BW B70C; C075799:ICI D2138; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D000109:Acetylcholine; D006918:Hydroxyurea; D007213:Indomethacin