PMID- 23220160
OWN - NLM
STAT- MEDLINE
DCOM- 20130902
LR  - 20131121
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 699
IP  - 1-3
DP  - 2013 Jan 15
TI  - Modulation of antigen-induced responses by serotonin and prostaglandin E2 via EP1 
      and EP4 receptors in the peripheral rat lung.
PG  - 141-9
LID - S0014-2999(12)00970-3 [pii]
LID - 10.1016/j.ejphar.2012.11.039 [doi]
AB  - 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.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Larsson-Callerfelt, Anna-Karin
AU  - Larsson-Callerfelt AK
AD  - Lung Biology, Department of Experimental Medical Science, Lund University, Lund 
      22184, Sweden. anna-karin_l.larsson@med.lu.se
FAU - Dahlen, Sven-Erik
AU  - Dahlen SE
FAU - Kuhl, Anna-Rebekka
AU  - Kuhl AR
FAU - Lex, Dennis
AU  - Lex D
FAU - Uhlig, Stefan
AU  - Uhlig S
FAU - Martin, Christian
AU  - Martin C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121203
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Antigens)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Receptors, Prostaglandin E, EP1 Subtype)
RN  - 0 (Receptors, Prostaglandin E, EP4 Subtype)
RN  - 333DO1RDJY (Serotonin)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Antigens/immunology
MH  - Bronchoconstriction/immunology
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Dinoprostone/immunology/*metabolism
MH  - Lung/immunology
MH  - Ovalbumin/immunology
MH  - Prostaglandin-Endoperoxide Synthases/immunology/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Prostaglandin E, EP1 Subtype/immunology/*metabolism
MH  - Receptors, Prostaglandin E, EP4 Subtype/immunology/*metabolism
MH  - Serotonin/*metabolism
EDAT- 2012/12/12 06:00
MHDA- 2013/09/03 06:00
CRDT- 2012/12/11 06:00
PHST- 2011/11/18 00:00 [received]
PHST- 2012/11/15 00:00 [revised]
PHST- 2012/11/23 00:00 [accepted]
PHST- 2012/12/11 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2013/09/03 06:00 [medline]
AID - S0014-2999(12)00970-3 [pii]
AID - 10.1016/j.ejphar.2012.11.039 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2013 Jan 15;699(1-3):141-9. doi: 10.1016/j.ejphar.2012.11.039. 
      Epub 2012 Dec 3.