Modulation of antigen-induced responses by serotonin and prostaglandin E₂ via EP₁ and EP₄ receptors in the peripheral rat lung

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• 作者：Anna-Karin Larsson-Callerfelt^a ; ^b ; ^{anna-karin_l.larsson@med.lu.se} ; Sven-Erik Dahlé ; n^b ; ^{sven-erik.dahlen@med.lu.se} ; Anna-Rebekka Kü ; hl^c ; ^{anna-rebekka.kuehl@uni-rostock.de} ; Dennis Lex^d ; ^{dlex@ukaachen.de} ; Stefan Uhlig^c ; ^d ; ^{suhlig@ukaachen.de} ; Christian Martin^c ; ^d ; ^{chmartin@ukaachen.de}
• 关键词：Airway smooth muscle ; Contraction ; Ovalbumin ; Precision-cut lung slices ; Prostaglandins ; Serotonin
• 刊名：European Journal of Pharmacology
• 出版年：2013
• 出版时间：15 January, 2013
• 年：2013
• 卷：699
• 期：1-3
• 页码：141-149
• 全文大小：490 K

文摘

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 EP₁ receptor antagonist ONO-8713 reduced the contractions, whereas the EP₄ 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 PGE₂ is the main prostanoid involved in the early allergic airway response in the rat lung. PGE₂ appears to act both as a primary mediator of antigen-induced airway contraction via the EP₄ receptor and as a downstream modulator of serotonin-induced bronchoconstriction via the EP₁ receptor.