Identification of a novel human ADP receptor coupled to Gi

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; coupled receptor displaying a high affinity for ADP, similar to the P2Y12 receptor and can therefore be tentatively called P2Y(13). In 1321N1 cells, the P2Y13 receptor coupled to the phosphoinositide pathway only when coexpressed with Gals. 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-polymerise 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.