Bell, Kathrin

Heinemann, Ákos

Kostenis, Evi

Platzer, Wolfgang

Schröder, Ralf

Sedej, Miriam

Waldhoer, Maria

BMC Pharmacology

English

PubMed

Miriam Sedej

Ralf Schröder

Kathrin Bell

Wolfgang Platzer

Evi Kostenis

Ákos Heinemann

Maria Waldhoer

Springer - Publisher Connector

MEETING ABSTRACT Open Access
The D-type prostanoid (DP) receptor enhances the
signaling of chemoattractant receptor-homologous
molecule expressed on Th2 cells (CRTH2)
Miriam Sedej1, Ralf Schröder2, Kathrin Bell2, Wolfgang Platzer1, Evi Kostenis2, Ákos Heinemann1, Maria Waldhoer1,3*
From 17th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint meeting with the
Hungarian Society of Experimental and Clinical Pharmacology (MFT)
Innsbruck, Austria. 29-30 September 2011
Background
Prostaglandin (PG) D2 is substantially involved in aller-
gic responses and signals via the seven-transmembrane-
spanning/G protein-coupled receptors, chemoattractant
receptor-homologous molecule expressed on Th2 cells
(CRTH2) and D-type prostanoid (DP) receptor. While
the proinflammatory function of CRTH2 is well recog-
nized and CRTH2 is hence considered as an important
emerging pharmacotherapeutic target, the role of the
DP receptor in mediating the biological effects of PGD2
in allergic inflammation has remained unclear.
Methods
The cross-talk of CRTH2 and DP receptors was investi-
gated using both a recombinant HEK293 cell model and
human eosinophils in Ca2+ mobilization assays, co-
immunoprecipitation and radioligand binding assays.
Results
We show that CRTH2 and DP receptors modulate each
other’s signalling properties and form CRTH2/DP het-
eromers without altering their ligand-binding capacities.
We find that the DP receptor amplifies the CRTH2-
induced Ca2+ release from intracellular stores and, coin-
cidentally, forfeits its own signalling potency. Moreover,
desensitization or pharmacological blockade of the DP
receptor hinders CRTH2-mediated signal transduction.
Pharmacological blockade of Gaq/11 proteins abolishes
the Ca2+ response to both CRTH2 and DP agonists,
while inhibition of Gai proteins selectively attenuates the
CRTH2-mediated response but not the DP signal.
Conclusions
Our data demonstrate the capacity of DP receptors to
amplify the biological response to CRTH2 activation.
Therefore, the CRTH2/DP heteromer may not only
represent a functional signalling unit for PGD2 but also
a potential target for development of heteromer-directed
therapies to treat allergic diseases.
Author details
1Institute of Experimental and Clinical Pharmacology, Medical University of
Graz, 8010 Graz, Austria. 2Institute of Pharmaceutical Biology, University of
Bonn, 53115 Bonn, Germany. 3Current address: Hagedorn Research Institute,
Novo Nordisk A/S, 2820 Gentofte, Denmark.
Published: 5 September 2011
doi:10.1186/1471-2210-11-S2-A58
Cite this article as: Sedej et al.: The D-type prostanoid (DP) receptor
enhances the signaling of chemoattractant receptor-homologous
molecule expressed on Th2 cells (CRTH2). BMC Pharmacology 2011 11(Suppl
2):A58.
* Correspondence: maria.waldhoer@medunigraz.at
1Institute of Experimental and Clinical Pharmacology, Medical University of
Graz, 8010 Graz, Austria
Full list of author information is available at the end of the article
Sedej et al. BMC Pharmacology 2011, 11(Suppl 2):A58
http://www.biomedcentral.com/1471-2210/11/S2/A58
© 2011 Sedej et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.


The D-type prostanoid (DP) receptor enhances the signaling of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2)

Crossref

file:///data/core-remote/dit/data/Springer-OA/pdf/78d/aHR0cDovL2xpbmsuc3ByaW5nZXIuY29tLzEwLjExODYvMTQ3MS0yMjEwLTExLVMyLUE1OC5wZGY=.pdf

The D-type prostanoid (DP) receptor enhances the signaling of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2)

Abstract

Similar works

Full text

Available Versions

Springer - Publisher Connector

Crossref

Springer - Publisher Connector