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This Article Full Text Full Text (PDF) All Versions of this Article: 287/5/L1035    most recent 00138.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Catalli, A. Articles by Janssen, L. J. Search for Related Content PubMed PubMed Citation Articles by Catalli, A. Articles by Janssen, L. J.

Augmentation of bovine airway smooth muscle responsiveness to carbachol, KCl, and histamine by the isoprostane 8-iso-PGE₂

¹Firestone Institute for Respiratory Health and the Father Sean O'Sullivan Research Center, St. Joseph's Hospital; and ²Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5

Submitted 13 April 2004 ; accepted in final form 14 July 2004

Isoprostanes are generated during periods of oxidative stress, which characterize diseases such as asthma and cystic fibrosis. They also elicit functional responses and may therefore contribute to the pathology of these diseases. We set out to examine the effects of isoprostanes on airway responsiveness to cholinergic stimulation. Muscle bath techniques were employed using isolated bovine tracheal smooth muscle. 8-Isoprostaglandin E₂ (8-iso-PGE₂) increased tone directly on its own, although the magnitude of this response, even at the highest concentration tested, was only a fraction of that evoked by KCl or carbachol. More importantly, though, pretreatment of the tissues with 8-iso-PGE₂ (10 µM) markedly augmented responses to submaximal and even subthreshold concentrations of KCl, carbachol, or histamine, whereas maximal responses to these agents were unaffected by the isoprostane. The augmentative effect on cholinergic responsiveness was mimicked by PGE₂ (0.1 µM) and by the FP agonists PGF₂ (0.1 µM) and fluprostenol (0.1 µM), but not by the EP₃ agonist sulprostone (0.1 µM) or the TP agonist U-46619 (0.1 µM). Antagonists of EP₁ receptors (AH-6809 and SC-19920, 10 µM) and TP receptors (ICI-192605, 1 µM) had no effect on 8-iso-PGE₂-induced augmentation of cholinergic responsiveness. We conclude that 8-iso-PGE₂ induces nonspecific airway smooth muscle hyperresponsiveness through a non-TP non-EP prostanoid receptor.

prostanoid receptors; contraction; asthma; oxidative stress; 8-isoprostaglandin E₂

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