Identification of a novel human ADP receptor coupled to G(i)

We have cloned and expressed a novel human G-protein-coupled receptor closely related to the human P2Y(12) receptor. It corresponds to the orphan receptor called GPR86. GPR86 proved to be a G(i)-coupled receptor displaying a high affinity for ADP, similar to the P2Y(12) receptor and can therefore be...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-11, Vol.276 (44), p.41479-41485
Main Authors: Communi, D, Gonzalez, N S, Detheux, M, Brézillon, S, Lannoy, V, Parmentier, M, Boeynaems, J M
Format: Article
Language:English
Subjects:
Adenosine Diphosphate - metabolism
Amino Acid Sequence
Animals
Base Sequence
CHO Cells
Cloning, Molecular
Cricetinae
DNA
GTP-Binding Protein alpha Subunits, Gi-Go - metabolism
Humans
Molecular Sequence Data
Protein Binding
Receptors, Purinergic P2 - chemistry
Receptors, Purinergic P2 - genetics
Receptors, Purinergic P2 - metabolism
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Summary:We have cloned and expressed a novel human G-protein-coupled receptor closely related to the human P2Y(12) receptor. It corresponds to the orphan receptor called GPR86. GPR86 proved to be a G(i)-coupled receptor displaying a high affinity for ADP, similar to the P2Y(12) receptor and can therefore be tentatively called P2Y(13). In 1321N1 cells, the P2Y(13) 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 P2Y(13) 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 P2Y(13) 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 P2Y(12) and P2Y(13) receptors form a subgroup of related P2Y subtypes that is structurally different from the other P2Y subtypes but share coupling to G(i) and a high affinity for ADP.
ISSN:0021-9258
DOI:10.1074/jbc.M105912200