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Modulation of antigen-induced responses by serotonin and prostaglandin E(2) via EP(1) and EP(4) receptors in the peripheral rat lung.

Larsson Callerfelt, Anna-Karin LU ; Dahlén, Sven-Erik; Kühl, Anna-Rebekka; Lex, Dennis; Uhlig, Stefan and Martin, Christian (2013) In European Journal of Pharmacology 699(1-3). p.141-149
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Contraction, Airway smooth muscle, Ovalbumin, Precision-cut lung slices, Prostaglandins, Serotonin
in
European Journal of Pharmacology
volume
699
issue
1-3
pages
141 - 149
publisher
Elsevier
external identifiers
  • wos:000314659600020
  • pmid:23220160
  • scopus:84871940768
ISSN
1879-0712
DOI
10.1016/j.ejphar.2012.11.039
language
English
LU publication?
yes
id
28157f97-09a0-4c3f-9eb4-5fd46ea7346c (old id 3347488)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23220160?dopt=Abstract
date added to LUP
2013-01-02 12:32:13
date last changed
2019-02-20 01:17:53
@article{28157f97-09a0-4c3f-9eb4-5fd46ea7346c,
  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.},
  author       = {Larsson Callerfelt, Anna-Karin and Dahlén, Sven-Erik and Kühl, Anna-Rebekka and Lex, Dennis and Uhlig, Stefan and Martin, Christian},
  issn         = {1879-0712},
  keyword      = {Contraction,Airway smooth muscle,Ovalbumin,Precision-cut lung slices,Prostaglandins,Serotonin},
  language     = {eng},
  number       = {1-3},
  pages        = {141--149},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Modulation of antigen-induced responses by serotonin and prostaglandin E(2) via EP(1) and EP(4) receptors in the peripheral rat lung.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2012.11.039},
  volume       = {699},
  year         = {2013},
}