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Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6
- Source :
- Scientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
- Publication Year :
- 2017
- Publisher :
- Nature Portfolio, 2017.
-
Abstract
- Abstract Cyclooxygenase-2 catalyses the biosynthesis of prostaglandins from arachidonic acid but also the biosynthesis of prostaglandin glycerol esters (PG-Gs) from 2-arachidonoylglycerol. Previous studies identified PG-Gs as signalling molecules involved in inflammation. Thus, the glyceryl ester of prostaglandin E2, PGE2-G, mobilizes Ca2+ and activates protein kinase C and ERK, suggesting the involvement of a G protein-coupled receptor (GPCR). To identify the endogenous receptor for PGE2-G, we performed a subtractive screening approach where mRNA from PGE2-G response-positive and -negative cell lines was subjected to transcriptome-wide RNA sequencing analysis. We found several GPCRs that are only expressed in the PGE2-G responder cell lines. Using a set of functional readouts in heterologous and endogenous expression systems, we identified the UDP receptor P2Y6 as the specific target of PGE2-G. We show that PGE2-G and UDP are both agonists at P2Y6, but they activate the receptor with extremely different EC50 values of ~1 pM and ~50 nM, respectively. The identification of the PGE2-G/P2Y6 pair uncovers the signalling mode of PG-Gs as previously under-appreciated products of cyclooxygenase-2.
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 7
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Scientific Reports
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.0c6b5a4f249e46d79caac5439349ac48
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41598-017-02414-8