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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.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Larsson-Callerfelt AK,Dahlén SE,Kühl AR,Lex D,Uhlig S,Martin C

doi

10.1016/j.ejphar.2012.11.039

subject

Has Abstract

pub_date

2013-01-15 00:00:00

pages

141-9

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(12)00970-3

journal_volume

699

pub_type

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