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Prostaglandin D(2) induces contractions through activation of TP receptors in peripheral lung tissue from the guinea pig.

Larsson Callerfelt, Anna-Karin LU ; Hagfjärd, Annika; Dahlén, Sven-Erik and Adner, Mikael (2011) In European Journal of Pharmacology 669(1-3). p.136-142
Abstract
Prostaglandin D(2) (PGD(2)), released through mast cell activation, is used as a non-invasive biomarker in patients with asthma. Since PGD(2) can elicit opposing effects on airway tone via activation of the PGD(2) receptors DP(1) and DP(2) as well as the thromboxane receptor TP, the aim of this study was to characterize the receptors that are activated by PGD(2) in the guinea pig lung parenchyma. PGD(2) and the thromboxane analog U46619 induced concentration-dependent contractions. U46619 was more potent and caused stronger effect than PGD(2). The specific TP receptor antagonist SQ-29548 and the combined TP and DP(2) receptor antagonist BAYu3405 concentration-dependently shifted the curves for both agonists to the right. The DP(1) receptor... (More)
Prostaglandin D(2) (PGD(2)), released through mast cell activation, is used as a non-invasive biomarker in patients with asthma. Since PGD(2) can elicit opposing effects on airway tone via activation of the PGD(2) receptors DP(1) and DP(2) as well as the thromboxane receptor TP, the aim of this study was to characterize the receptors that are activated by PGD(2) in the guinea pig lung parenchyma. PGD(2) and the thromboxane analog U46619 induced concentration-dependent contractions. U46619 was more potent and caused stronger effect than PGD(2). The specific TP receptor antagonist SQ-29548 and the combined TP and DP(2) receptor antagonist BAYu3405 concentration-dependently shifted the curves for both agonists to the right. The DP(1) receptor agonist BW245 induced a weak relaxation at high concentrations, whereas the DP(1) receptor antagonist BWA868C did not affect the PGD(2) induced contractions. The specific DP(2) receptor agonist 13,14-dihydro-15-keto-PGD(2) showed neither contractile nor relaxant effect in the parenchyma. Furthermore, studies in precision-cut lung slices specified that airways as well as pulmonary arteries and veins contracted to both PGD(2) and U46619. When the lung parenchyma from ovalbumin sensitized guinea pigs were exposed to ovalbumin, both thromboxane B(2) and PGD(2) were released. Ovalbumin also induced maximal contractions at similar level as PGD(2) in the parenchyma, which was partly reduced by SQ-29548. These data show that PGD(2) should be recognized as a TP receptor agonist in the peripheral lung inducing contraction on airways, arteries and veins. Therefore, a TP receptor antagonist can be useful in combination treatment of allergic responses in asthma. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Lung parenchyma, Guinea pig, Ovalbumin, Precision cut lung slice, Prostaglandin D-2, Thromboxane
in
European Journal of Pharmacology
volume
669
issue
1-3
pages
136 - 142
publisher
Elsevier
external identifiers
  • wos:000296989500020
  • pmid:21872585
  • scopus:80053337010
ISSN
1879-0712
DOI
10.1016/j.ejphar.2011.07.046
language
English
LU publication?
yes
id
f73c3b22-3c73-401a-bb72-b20d4bc33abf (old id 2168539)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21872585?dopt=Abstract
date added to LUP
2011-10-03 13:44:17
date last changed
2017-08-06 03:05:35
@article{f73c3b22-3c73-401a-bb72-b20d4bc33abf,
  abstract     = {Prostaglandin D(2) (PGD(2)), released through mast cell activation, is used as a non-invasive biomarker in patients with asthma. Since PGD(2) can elicit opposing effects on airway tone via activation of the PGD(2) receptors DP(1) and DP(2) as well as the thromboxane receptor TP, the aim of this study was to characterize the receptors that are activated by PGD(2) in the guinea pig lung parenchyma. PGD(2) and the thromboxane analog U46619 induced concentration-dependent contractions. U46619 was more potent and caused stronger effect than PGD(2). The specific TP receptor antagonist SQ-29548 and the combined TP and DP(2) receptor antagonist BAYu3405 concentration-dependently shifted the curves for both agonists to the right. The DP(1) receptor agonist BW245 induced a weak relaxation at high concentrations, whereas the DP(1) receptor antagonist BWA868C did not affect the PGD(2) induced contractions. The specific DP(2) receptor agonist 13,14-dihydro-15-keto-PGD(2) showed neither contractile nor relaxant effect in the parenchyma. Furthermore, studies in precision-cut lung slices specified that airways as well as pulmonary arteries and veins contracted to both PGD(2) and U46619. When the lung parenchyma from ovalbumin sensitized guinea pigs were exposed to ovalbumin, both thromboxane B(2) and PGD(2) were released. Ovalbumin also induced maximal contractions at similar level as PGD(2) in the parenchyma, which was partly reduced by SQ-29548. These data show that PGD(2) should be recognized as a TP receptor agonist in the peripheral lung inducing contraction on airways, arteries and veins. Therefore, a TP receptor antagonist can be useful in combination treatment of allergic responses in asthma.},
  author       = {Larsson Callerfelt, Anna-Karin and Hagfjärd, Annika and Dahlén, Sven-Erik and Adner, Mikael},
  issn         = {1879-0712},
  keyword      = {Lung parenchyma,Guinea pig,Ovalbumin,Precision cut lung slice,Prostaglandin D-2,Thromboxane},
  language     = {eng},
  number       = {1-3},
  pages        = {136--142},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Prostaglandin D(2) induces contractions through activation of TP receptors in peripheral lung tissue from the guinea pig.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2011.07.046},
  volume       = {669},
  year         = {2011},
}