laropiprant attenuates ep3 and tp prostanoid receptor-mediated thrombus formation
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MEETING ABSTRACT Open Access
Laropiprant attenuates EP3 and TP prostanoidreceptor-mediated thrombus formationSonia Philipose1, Viktória Kónya1, Mirjana Lazarević1, Lisa M Pasterk1, Gunther Marsche1, Sasa Frank2,Bernhard A Peskar1, Ákos Heinemann1*, Rufina Schuligoi1
From 18th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint meeting with theCroatian, Serbian and Slovenian Pharmacological Societies.Graz, Austria. 20-21 September 2012
BackgroundThe use of the lipid-lowering agent niacin is hampered bya frequent flush response which is largely mediated byprostaglandin (PG) D2. Therefore, concomitant adminis-tration of the D-type prostanoid (DP) receptor antagonistlaropiprant has been proposed to be a useful approach inpreventing niacin-induced flush. However, antagonizingPGD2, which is a potent inhibitor of platelet aggregation,might pose the risk of atherothrombotic events in cardio-vascular disease. Therefore, we investigated the effects oflaropiorant on platelet function.
MethodsPlatelet aggregation assays were performed ex vivo using aplatelet aggregation analyser (Aggregometer II). Bloodfrom healthy human donors was used to obtain platelet-rich plasma. The expression of P-selectin and activation ofglycoprotein IIb/IIIa was examined using CD62P andPAC1 antibodies, respectively, by direct flow cytometry.In vitro thrombus formation was assessed by flowing wholeblood on collagen-coated Cellix biochips at −30 dyn/cm2
using the Mirus nanopump.
ResultsIn vitro treatment of platelets with laropiprant preventedthe inhibitory effects of PGD2 on platelet function, i.e.platelet aggregation, P-selectin expression, activation ofglycoprotein IIb/IIIa and thrombus formation. In con-trast, laropiprant did not prevent the inhibitory effects ofacetylsalicylic acid or niacin on thrombus formation. Athigher concentrations, laropiprant by itself attenuated
platelet activation induced by thromboxane (TP) andE-type prostanoid (EP)-3 receptor stimulation, as demon-strated in assays of platelet aggregation, P-selectinexpression, and activation of glycoprotein IIb/IIIa. Inhibi-tion of platelet function exerted by EP4 or I-type prosta-noid (IP) receptors was not affected by laropiprant.
ConclusionsThese in vitro data suggest that niacin/laropiprant forthe treatment of dyslipidemias might have a beneficialprofile with respect to platelet function and thromboticevents in vascular disease.
AcknowledgementsS.P. was funded by the PhD Program Molecular Medicine of the MedicalUniversity of Graz. This study was supported by the Jubiläumsfonds of theAustrian National Bank (OeNB, grants 13487 and 14263) and the AustrianScience Fund (FWF; grants P22521-B18, P19473-B05, P21004-B02 andP22976-B18).
Author details1Institute of Experimental and Clinical Pharmacology, Medical University ofGraz, 8010 Graz Austria. 2Institute of Molecular Biology and Biochemistry,Medical University of Graz, 8010 Graz, Austria.
Published: 17 September 2012
doi:10.1186/2050-6511-13-S1-A14Cite this article as: Philipose et al.: Laropiprant attenuates EP3 and TPprostanoid receptor-mediated thrombus formation. BMC Pharmacologyand Toxicology 2012 13(Suppl 1):A14.
* Correspondence: [email protected] of Experimental and Clinical Pharmacology, Medical University ofGraz, 8010 Graz AustriaFull list of author information is available at the end of the article
Philipose et al. BMC Pharmacology and Toxicology 2012, 13(Suppl 1):A14http://www.biomedcentral.com/2050-6511/13/S1/A14
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