title: Modulation of antigen-induced responses by serotonin and prostaglandin E2 via EP1 and EP4 receptors in the peripheral rat lung.
abstract: The cyclooxygenase (COX) pathway and prostanoids may critically contribute to the early allergic airway response. In the rat lung, serotonin (5-HT) is a major mediator of antigen-induced contractions. The aim of this study was therefore to examine the relative role of the COX pathway and serotonin for antigen-induced contractions in the rat lung. Airway responses were studied in rat precision-cut lung slices (PCLS). Lung slices were stimulated with ovalbumin or serotonin after pretreatment with COX inhibitors or specific TP or EP receptor antagonists. Changes in airway size (contractions/relaxations) were measured by a digital video camera. The supernatants were analysed for changes in prostaglandin and serotonin release. Airway contractions to ovalbumin were attenuated by the unselective COX inhibitor indomethacin, the selective COX-1 inhibitor FR-122047 and COX-2 inhibitor celecoxib. The EP(1) receptor antagonist ONO-8713 reduced the contractions, whereas the EP(4) receptor antagonist L-161,982 significantly increased the contractile response to ovalbumin. The 5-HT(2A) receptor antagonist ketanserin completely inhibited the ovalbumin-induced contractions. The different COX inhibitors decreased the production of prostaglandins but did not affect the synthesis of serotonin. The serotonin-induced bronchoconstriction was attenuated by celecoxib and ONO-8713, but not by methacholine. Taken together, our data indicate that PGE(2) is the main prostanoid involved in the early allergic airway response in the rat lung. PGE(2) appears to act both as a primary mediator of antigen-induced airway contraction via the EP(4) receptor and as a downstream modulator of serotonin-induced bronchoconstriction via the EP(1) receptor.
authors.affiliation: Lung Biology, Department of Experimental Medical Science, Lund University, Lund 22184, Sweden. anna-karin_l.larsson@med.lu.se
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Larsson-Callerfelt
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Dahlén
authors.forename: Anna-Rebekka
authors.initials: AR
authors.lastname: Kühl
authors.forename: Dennis
authors.initials: D
authors.lastname: Lex
authors.forename: Stefan
authors.initials: S
authors.lastname: Uhlig
authors.forename: Christian
authors.initials: C
authors.lastname: Martin
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D016084:Bronchoconstriction / Q000276:immunology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000276:immunology / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000276:immunology / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
chemical_list: D000941:Antigens; D016861:Cyclooxygenase Inhibitors; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012701:Serotonin; D010047:Ovalbumin; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone