Identification of a novel human ADP receptor coupled to Gi
Identification of a novel human ADP receptor coupled to Gi
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DOI：
10.1074/jbc.m105912200
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发表时间：
2001-11-02
影响因子：
4.8
通讯作者：
Boeynaems, JM
中科院分区：
文献类型：
--
作者：
Communi, D;Gonzalez, NS;Boeynaems, JM
我们克隆并表达了一种与人类 P2Y(12) 受体密切相关的新型人类 G 蛋白偶联受体。它对应于称为 GPR86 的孤儿受体。 GPR86被证明是G；偶联受体对 ADP 表现出高亲和力，类似于 P2Y12 受体，因此可暂称为 P2Y(13)。在 1321N1 细胞中，P2Y13 受体仅在与 Gals 共表达时才与磷酸肌醇途径偶联。纳摩尔浓度的 ADP 和 2MeSADP 可同等刺激肌醇三磷酸的形成，而 2MeSATP 和 ATP 则无活性。在表达 P2Y13 受体的 CHO-K1 细胞中，ADP 和 2MeSADP 对毛喉素刺激的 cAMP 积累具有双相作用：纳摩尔浓度下的抑制作用和微摩尔浓度下的增强作用。在相同的细胞中，ADP 和 2MeSADP 还以百日咳毒素敏感的方式刺激 Erk1 和 Erk2 的磷酸化。通过逆转录酶-聚合酶链式反应研究P2Y13的组织分布，并在脾脏和脑中获得了主要信号。虽然这些可以通过组织分布和一些药理学特征来区分，但 P2Y12 和 P2Y13 受体形成相关 P2Y 亚型的一个亚组，其在结构上与其他 P2Y 亚型不同，但与 Gi 偶联且与 ADP 具有高亲和力。
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.