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Originally published In Press as doi:10.1074/jbc.M105912200 on August 23, 2001

J. Biol. Chem., Vol. 276, Issue 44, 41479-41485, November 2, 2001
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Identification of a Novel Human ADP Receptor Coupled to Gi*

Didier CommuniDagger §, Nathalie Suarez GonzalezDagger , Michel Detheux||, Stéphane Brézillon||, Vincent Lannoy||, Marc ParmentierDagger , and Jean-Marie BoeynaemsDagger **

From the Dagger  Institute of Interdisciplinary Research, School of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium, || Euroscreen, 802 Route de Lennik, 1070 Brussels, Belgium, and the ** Department of Medical Chemistry, Erasme Hospital, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium

We have cloned and expressed a novel human G-protein-coupled receptor closely related to the human P2Y12 receptor. It corresponds to the orphan receptor called GPR86. GPR86 proved to be a Gi-coupled receptor displaying a high affinity for ADP, similar to the P2Y12 receptor and can therefore be tentatively called P2Y13. In 1321N1 cells, the P2Y13 receptor coupled to the phosphoinositide pathway only when coexpressed with Galpha 16. Inositol trisphosphate formation was stimulated equipotently by nanomolar concentrations of ADP and 2MeSADP, whereas 2MeSATP and ATP were inactive. In CHO-K1 cells expressing the P2Y13 receptor, ADP and 2MeSADP had a biphasic effect on the forskolin-stimulated accumulation of cAMP: inhibition at nanomolar concentrations and potentiation at micromolar levels. In the same cells, ADP and 2MeSADP also stimulated the phosphorylation of Erk1 and Erk2, in a pertussis toxin-sensitive way. The tissue distribution of P2Y13 was investigated by reverse transcriptase-polymerase chain reaction, and the predominant signals were obtained in spleen and brain. Although these can be discriminated by tissue distribution and some pharmacological features, the P2Y12 and P2Y13 receptors form a subgroup of related P2Y subtypes that is structurally different from the other P2Y subtypes but share coupling to Gi and a high affinity for ADP.

* This work was supported by an Action de Recherche Concertée of the Communauté Française de Belgique, by the Belgian Program on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister's Office, Federal Service for Science, Technology and Culture, by grants from the Fonds de la Recherche Scientifique Médicale, the Bekales Fundation, EU Grant QLK3-2000-00237, the Fondation Médicale Reine Elisabeth, and Boehringer Ingelheim, and the Fonds Emile DEFAY.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF406692.

§ Chargé de Recherches of the Fonds National de la Recherche Scientifique. To whom correspondence should be addressed: Inst. of Interdisciplinary Research, Campus Erasme, Building C, 5th floor (local C5-145), 808, Route de Lennik, 1070 Brussels, Belgium. Tel.: 32-2-555.41.76; Fax: 32-2-555.46.55; E-mail: communid@ulb.ac.be.

Supported by grants from Euroscreen.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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