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Sphingosine 1-phosphate and dioleoylphosphatidic acid are low affinity agonists for the orphan receptor GPR63

Five high affinity G-protein-coupled receptors for sphingosine 1-phosphate (S1P) have been characterised so far (S1P 1,2,3,4,5 formerly referred to as edg1,5,3,6,8). In this study, we show that S1P, dihydro-sphingosine 1-phosphate (dihydro-S1P) and dioleoylphosphatidic acid (doPA) are agonists for t...

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Bibliographic Details
Published in:Cellular signalling 2003-04, Vol.15 (4), p.435-446
Main Authors: Niedernberg, Anke, Tunaru, Sorin, Blaukat, Andree, Ardati, Ali, Kostenis, Evi
Format: Article
Language:English
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Summary:Five high affinity G-protein-coupled receptors for sphingosine 1-phosphate (S1P) have been characterised so far (S1P 1,2,3,4,5 formerly referred to as edg1,5,3,6,8). In this study, we show that S1P, dihydro-sphingosine 1-phosphate (dihydro-S1P) and dioleoylphosphatidic acid (doPA) are agonists for the orphan receptor GPR63. All three phospholipids mobilise intracellular calcium in CHO cells transiently transfected with GPR63. Calcium signals required cotransfection of a chimeric Gα q/i protein in a fluorometric imaging plate reader (FLIPR™) assay but did not require overexpressed G proteins in an aequorin assay, using a green fluorescent protein (GFP)–aequorin fusion protein as a bioluminescent Ca 2+ reporter. GPR63 expression in CHO cells confers proliferative responses to S1P in a pertussis toxin (PTX)-insensitive manner. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) indicated highest expression in brain, especially in the thalamus and the nucleus caudatus. In peripheral tissues, highest expression was observed in thymus, stomach and small intestine; lower abundance of transcripts was detected in kidney, spleen, pancreas and heart. The discovery that S1P, dihydro-S1P and dioleoylphosphatidic acid activate GPR63 will facilitate the identification of agonists and antagonists, and help to unravel the biological function of this receptor.
ISSN:0898-6568
1873-3913
DOI:10.1016/S0898-6568(02)00119-5